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Patterning of the cell cortex by Rho GTPases

Nature Reviews Molecular Cell Biology volume 25, pages 290–308 (2024)Cite this article

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A Publisher Correction to this article was published on 15 January 2024

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Abstract

The Rho GTPases — RHOA, RAC1 and CDC42 — are small GTP binding proteins that regulate basic biological processes such as cell locomotion, cell division and morphogenesis by promoting cytoskeleton-based changes in the cell cortex. This regulation results from active (GTP-bound) Rho GTPases stimulating target proteins that, in turn, promote actin assembly and myosin 2-based contraction to organize the cortex. This basic regulatory scheme, well supported by in vitro studies, led to the natural assumption that Rho GTPases function in vivo in an essentially linear matter, with a given process being initiated by GTPase activation and terminated by GTPase inactivation. However, a growing body of evidence based on live cell imaging, modelling and experimental manipulation indicates that Rho GTPase activation and inactivation are often tightly coupled in space and time via signalling circuits and networks based on positive and negative feedback. In this Review, we present and discuss this evidence, and we address one of the fundamental consequences of coupled activation and inactivation: the ability of the Rho GTPases to self-organize, that is, direct their own transition from states of low order to states of high order. We discuss how Rho GTPase self-organization results in the formation of diverse spatiotemporal cortical patterns such as static clusters, oscillatory pulses, travelling wave trains and ring-like waves. Finally, we discuss the advantages of Rho GTPase self-organization and pattern formation for cell function.

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Fig. 1: Basic principles of Rho GTPase regulation.
Fig. 2: Self-organizing Rho GTPase patterns.
Fig. 3: Feedback to Rho GTPase GEFs and GAPs.
Fig. 4: Proposed feedbacks for examples of self-organization.

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References

  1. Hodge, R. G. & Ridley, A. J. Regulating Rho GTPases and their regulators. Nat. Rev. Mol. Cell Biol. 17, 496–510 (2016).

    Article  CAS  PubMed  Google Scholar 

  2. Jaffe, A. B. & Hall, A. Rho GTPases: biochemistry and biology. Annu. Rev. Cell Dev. Biol. 21, 247–269 (2005).

    Article  CAS  PubMed  Google Scholar 

  3. Scheffzek, K. & Ahmadian, M. R. GTPase activating proteins: structural and functional insights 18 years after discovery. Cell Mol. Life Sci. 62, 3014–3038 (2005).

    Article  CAS  PubMed  Google Scholar 

  4. Rossman, K. L., Der, C. J. & Sondek, J. GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factors. Nat. Rev. Mol. Cell Biol. 6, 167–180 (2005).

    Article  CAS  PubMed  Google Scholar 

  5. Michaud, A. et al. Cortical excitability and cell division. Curr. Biol. 31, R553–R559 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Allen, W. E., Zicha, D., Ridley, A. J. & Jones, G. E. A role for Cdc42 in macrophage chemotaxis. J. Cell Biol. 141, 1147–1157 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Kishi, K., Sasaki, T., Kuroda, S., Itoh, T. & Takai, Y. Regulation of cytoplasmic division of Xenopus embryo by rho p21 and its inhibitory GDP/GTP exchange protein (rho GDI). J. Cell Biol. 120, 1187–1195 (1993).

    Article  CAS  PubMed  Google Scholar 

  8. Massol, P., Montcourrier, P., Guillemot, J. C. & Chavrier, P. Fc receptor-mediated phagocytosis requires CDC42 and Rac1. EMBO J. 17, 6219–6229 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Stowers, L., Yelon, D., Berg, L. J. & Chant, J. Regulation of the polarization of T cells toward antigen-presenting cells by Ras-related GTPase CDC42. Proc. Natl Acad. Sci. USA 92, 5027–5031 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Barrett, K., Leptin, M. & Settleman, J. The Rho GTPase and a putative RhoGEF mediate a signaling pathway for the cell shape changes in Drosophila gastrulation. Cell 91, 905–915 (1997).

    Article  CAS  PubMed  Google Scholar 

  11. Howell, A. S. et al. Singularity in polarization: rewiring yeast cells to make two buds. Cell 139, 731–743 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Das, M. et al. Oscillatory dynamics of Cdc42 GTPase in the control of polarized growth. Science 337, 239–243 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Michaux, J. B., Robin, F. B., McFadden, W. M. & Munro, E. M. Excitable RhoA dynamics drive pulsed contractions in the early C. elegans embryo. J. Cell Biol. 217, 4230–4252 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Abreu-Blanco, M. T., Verboon, J. M. & Parkhurst, S. M. Coordination of Rho family GTPase activities to orchestrate cytoskeleton responses during cell wound repair. Curr. Biol. 24, 144–155 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Bement, W. M. et al. Activator-inhibitor coupling between Rho signalling and actin assembly makes the cell cortex an excitable medium. Nat. Cell Biol. 17, 1471–1483 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Bischof, J. et al. A cdk1 gradient guides surface contraction waves in oocytes. Nat. Commun. 8, 849 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  17. Burkel, B. M., Benink, H. A., Vaughan, E. M., von Dassow, G. & Bement, W. M. A Rho GTPase signal treadmill backs a contractile array. Dev. Cell 23, 384–396 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Graessl, M. et al. An excitable Rho GTPase signaling network generates dynamic subcellular contraction patterns. J. Cell Biol. 216, 4271–4285 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Wu, M., Wu, X. & De Camilli, P. Calcium oscillations-coupled conversion of actin travelling waves to standing oscillations. Proc. Natl Acad. Sci. USA 110, 1339–1344 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Xiao, S., Tong, C., Yang, Y. & Wu, M. Mitotic cortical waves predict future division sites by encoding positional and size information. Dev. Cell 43, 493–506.e3 (2017).

    Article  CAS  PubMed  Google Scholar 

  21. Landino, J. et al. Rho and F-actin self-organize within an artificial cell cortex. Curr. Biol. 31, 5613–5621.e5 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Ozbudak, E. M., Becskei, A. & van Oudenaarden, A. A system of counteracting feedback loops regulates Cdc42p activity during spontaneous cell polarization. Dev. Cell 9, 565–571 (2005).

    Article  CAS  PubMed  Google Scholar 

  23. Bement, W. M., Benink, H. A. & von Dassow, G. A microtubule-dependent zone of active RhoA during cleavage plane specification. J. Cell Biol. 170, 91–101 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Benink, H. A. & Bement, W. M. Concentric zones of active RhoA and Cdc42 around single cell wounds. J. Cell Biol. 168, 429–439 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Sokac, A. M., Co, C., Taunton, J. & Bement, W. Cdc42-dependent actin polymerization during compensatory endocytosis in Xenopus eggs. Nat. Cell Biol. 5, 727–732 (2003).

    Article  CAS  PubMed  Google Scholar 

  26. Nalbant, P., Hodgson, L., Kraynov, V., Toutchkine, A. & Hahn, K. M. Activation of endogenous Cdc42 visualized in living cells. Science 305, 1615–1619 (2004).

    Article  CAS  PubMed  Google Scholar 

  27. Machacek, M. et al. Coordination of Rho GTPase activities during cell protrusion. Nature 461, 99–103 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Somers, W. G. & Saint, R. A RhoGEF and Rho family GTPase-activating protein complex links the contractile ring to cortical microtubules at the onset of cytokinesis. Dev. Cell 4, 29–39 (2003).

    Article  CAS  PubMed  Google Scholar 

  29. Bement, W. M., Miller, A. L. & von Dassow, G. Rho GTPase activity zones and transient contractile arrays. Bioessays 28, 983–993 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Goryachev, A. B. & Pokhilko, A. V. Computational model explains high activity and rapid cycling of Rho GTPases within protein complexes. PLoS Comput. Biol. 2, e172 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  31. Clay, M. R. & Halloran, M. C. Rho activation is apically restricted by Arhgap1 in neural crest cells and drives epithelial-to-mesenchymal transition. Development 140, 3198–3209 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Mason, F. M., Xie, S., Vasquez, C. G., Tworoger, M. & Martin, A. C. RhoA GTPase inhibition organizes contraction during epithelial morphogenesis. J. Cell Biol. 214, 603–617 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Budnar, S. et al. Anillin promotes cell contractility by cyclic resetting of RhoA residence kinetics. Dev. Cell 49, 894–906.e12 (2019).

    Article  CAS  PubMed  Google Scholar 

  34. Bendezu, F. O. et al. Spontaneous Cdc42 polarization independent of GDI-mediated extraction and actin-based trafficking. PLoS Biol. 13, e1002097 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  35. van Bruggen, R., Anthony, E., Fernandez-Borja, M. & Roos, D. Continuous translocation of Rac2 and the NADPH oxidase component p67phox during phagocytosis. J. Biol. Chem. 279, 9097–9102 (2004).

    Article  PubMed  Google Scholar 

  36. Goryachev, A. B. & Pokhilko, A. V. Dynamics of Cdc42 network embodies a turing-type mechanism of yeast cell polarity. FEBS Lett. 582, 1437–1443 (2008).

    Article  CAS  PubMed  Google Scholar 

  37. Tatebe, H., Nakano, K., Maximo, R. & Shiozaki, K. Pom1 DYRK regulates localization of the Rga4 GAP to ensure bipolar activation of Cdc42 in fission yeast. Curr. Biol. 18, 322–330 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Simões, S. et al. Compartmentalisation of Rho regulators directs cell invagination during tissue morphogenesis. Development 133, 4257–4267 (2006).

    Article  PubMed  Google Scholar 

  39. di Pietro, F. et al. Systematic analysis of RhoGEF/GAP localizations uncovers regulators of mechanosensing and junction formation during epithelial cell division. Curr. Biol. 33, 858–874.e7 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  40. Müller, P. M. et al. Systems analysis of RhoGEF and RhoGAP regulatory proteins reveals spatially organized RAC1 signalling from integrin adhesions. Nat. Cell Biol. 22, 498–511 (2020).

    Article  PubMed  Google Scholar 

  41. Allard, J. & Mogilner, A. Traveling waves in actin dynamics and cell motility. Curr. Opin. Cell Biol. 25, 107–115 (2013).

    Article  CAS  PubMed  Google Scholar 

  42. Goryachev, A. B., Leda, M., Miller, A. L., von Dassow, G. & Bement, W. M. How to make a static cytokinetic furrow out of traveling excitable waves. Small GTPases 7, 65–70 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  43. Landge, A. N., Jordan, B. M., Diego, X. & Müller, P. Pattern formation mechanisms of self-organizing reaction-diffusion systems. Dev. Biol. 460, 2–11 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Mitchison, T. J. & Field, C. M. Self-organization of cellular units. Annu. Rev. Cell Dev. Biol. 37, 23–41 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Valdez, V. A., Neahring, L., Petry, S. & Dumont, S. Mechanisms underlying spindle assembly and robustness. Nat. Rev. Mol. Cell Biol. 24, 523–542 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Heald, R. et al. Self-organization of microtubules into bipolar spindles around artificial chromosomes in Xenopus egg extracts. Nature 382, 420–425 (1996).

    Article  CAS  PubMed  Google Scholar 

  47. Collinet, C. & Lecuit, T. Programmed and self-organized flow of information during morphogenesis. Nat. Rev. Mol. Cell Biol. 22, 245–265 (2021).

    Article  CAS  PubMed  Google Scholar 

  48. Hansen, S. D. et al. Stochastic geometry sensing and polarization in a lipid kinase–phosphatase competitive reaction. Proc. Natl Acad. Sci. USA 116, 15013–15022 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Murray, J. D. Mathematical Biology 19 (Springer-Verlag, 1993).

  50. Meinhardt, H. & Gierer, A. Pattern formation by local self-activation and lateral inhibition. Bioessays 22, 753–760 (2000).

    Article  CAS  PubMed  Google Scholar 

  51. Rao, C. V., Wolf, D. M. & Arkin, A. P. Control, exploitation and tolerance of intracellular noise. Nature 420, 231–237 (2002).

    Article  CAS  PubMed  Google Scholar 

  52. Chiou, J.-g, Moran, K. D. & Lew, D. J. How cells determine the number of polarity sites. Preprint at bioRxiv https://doi.org/10.1101/2020.05.21.109520 (2020).

  53. Hennig, K. et al. Stick–slip dynamics of cell adhesion triggers spontaneous symmetry breaking and directional migration of mesenchymal cells on one-dimensional lines. Sci. Adv. 6, eaau5670 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Lavrsen, K. et al. Microtubule detyrosination drives symmetry breaking to polarize cells for directed cell migration. Proc. Natl Acad. Sci. USA 120, e2300322120 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Hoyle, R. Pattern Formation (Cambridge Univ. Press, 2006).

  56. Cross, M. C. & Greenside, H. Pattern Formation and Dynamics in Nonequilibrium Systems (Cambridge Univ. Press, 2009).

  57. Miller, A. L. & Bement, W. M. Regulation of cytokinesis by Rho GTPase flux. Nat. Cell Biol. 11, 71–77 (2009).

    Article  CAS  PubMed  Google Scholar 

  58. Zheng, Y., Bender, A. & Cerione, R. A. Interactions among proteins involved in bud-site selection and bud-site assembly in Saccharomyces cerevisiae. J. Biol. Chem. 270, 626–630 (1995).

    Article  CAS  PubMed  Google Scholar 

  59. Loose, M., Fischer-Friedrich, E., Ries, J., Kruse, K. & Schwille, P. Spatial regulators for bacterial cell division self-organize into surface waves in vitro. Science 320, 789–792 (2008).

    Article  CAS  PubMed  Google Scholar 

  60. Ramm, B., Glock, P. & Schwille, P. In vitro reconstitution of self-organizing protein patterns on supported lipid bilayers. J. Vis. Exp. 28, 58139 (2018).

    Google Scholar 

  61. Cezanne, A., Lauer, J., Solomatina, A., Sbalzarini, I. F. & Zerial, M. A non-linear system patterns Rab5 GTPase on the membrane. eLife 9, e54434 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Goryachev, A. B. & Leda, M. Autoactivation of small GTPases by the GEF-effector positive feedback modules. F1000Res 8, https://doi.org/10.12688/f1000research.20003.1 (2019).

  63. Jackson, C. L. GEF–effector interactions. Cell Logist. 4, e943616 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  64. Horiuchi, H. et al. A novel Rab5 GDP/GTP exchange factor complexed to Rabaptin-5 links nucleotide exchange to effector recruitment and function. Cell 90, 1149–1159 (1997).

    Article  CAS  PubMed  Google Scholar 

  65. Grosshans, B. L., Ortiz, D. & Novick, P. Rabs and their effectors: achieving specificity in membrane traffic. Proc. Natl Acad. Sci. USA 103, 11821–11827 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Chen, Z. et al. Activated RhoA binds to the pleckstrin homology (PH) domain of PDZ-RhoGEF, a potential site for autoregulation. J. Biol. Chem. 285, 21070–21081 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Medina, F. et al. Activated RhoA is a positive feedback regulator of the Lbc family of Rho guanine nucleotide exchange factor proteins. J. Biol. Chem. 288, 11325–11333 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Chen, M. et al. Structure and regulation of human epithelial cell transforming 2 protein. Proc. Natl Acad. Sci. USA 117, 1027–1035 (2020).

    Article  CAS  PubMed  Google Scholar 

  69. Lin, Q., Yang, W., Baird, D., Feng, Q. & Cerione, R. A. Identification of a DOCK180-related guanine nucleotide exchange factor that is capable of mediating a positive feedback activation of Cdc42. J. Biol. Chem. 281, 35253–35262 (2006).

    Article  CAS  PubMed  Google Scholar 

  70. Bose, I. et al. Assembly of scaffold-mediated complexes containing Cdc42p, the exchange factor Cdc24p, and the effector Cla4p required for cell cycle-regulated phosphorylation of Cdc24p. J. Biol. Chem. 276, 7176–7186 (2001).

    Article  CAS  PubMed  Google Scholar 

  71. Butty, A. C. et al. A positive feedback loop stabilizes the guanine-nucleotide exchange factor Cdc24 at sites of polarization. EMBO J. 21, 1565–1576 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Hussain, N. K. et al. Endocytic protein intersectin-l regulates actin assembly via Cdc42 and N-WASP. Nat. Cell Biol. 3, 927–932 (2001).

    Article  CAS  PubMed  Google Scholar 

  73. Lamas, I., Weber, N. & Martin, S. G. Activation of Cdc42 GTPase upon CRY2-induced cortical recruitment is antagonized by GAPs in fission yeast. Cells 9, 2089 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. McGavin, M. K. et al. The intersectin 2 adaptor links Wiskott Aldrich syndrome protein (WASp)-mediated actin polymerization to T cell antigen receptor endocytosis. J. Exp. Med. 194, 1777–1787 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Castro-Castro, A. et al. Coronin 1A promotes a cytoskeletal-based feedback loop that facilitates Rac1 translocation and activation. EMBO J. 30, 3913–3927 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Segal, D., Zaritsky, A., Schejter, E. D. & Shilo, B. Z. Feedback inhibition of actin on Rho mediates content release from large secretory vesicles. J. Cell Biol. 217, 1815–1826 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Nguyen, T. T. et al. PLEKHG3 enhances polarized cell migration by activating actin filaments at the cell front. Proc. Natl Acad. Sci. USA 113, 10091–10096 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. DerMardirossian, C., Schnelzer, A. & Bokoch, G. M. Phosphorylation of RhoGDI by Pak1 mediates dissociation of Rac GTPase. Mol. Cell 15, 117–127 (2004).

    Article  CAS  PubMed  Google Scholar 

  79. Kitzing, T. M. et al. Positive feedback between Dia1, LARG, and RhoA regulates cell morphology and invasion. Genes. Dev. 21, 1478–1483 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Priya, R. et al. Feedback regulation through myosin II confers robustness on RhoA signalling at E-cadherin junctions. Nat. Cell Biol. 17, 1282–1293 (2015).

    Article  CAS  PubMed  Google Scholar 

  81. Barrows, D. et al. p21-activated kinases (PAKs) mediate the phosphorylation of PREX2 protein to initiate feedback inhibition of Rac1 GTPase. J. Biol. Chem. 290, 28915–28931 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Radu, M. et al. ArhGAP15, a Rac-specific GTPase-activating protein, plays a dual role in inhibiting small GTPase signaling. J. Biol. Chem. 288, 21117–21125 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Dibus, M., Brábek, J. & Rösel, D. A screen for PKN3 substrates reveals an activating phosphorylation of ARHGAP18. Int J. Mol. Sci. 21, 7769 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Diring, J., Mouilleron, S., McDonald, N. Q. & Treisman, R. RPEL-family rhoGAPs link Rac/Cdc42 GTP loading to G-actin availability. Nat. Cell Biol. 21, 845–855 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Lee, C. S., Choi, C. K., Shin, E. Y., Schwartz, M. A. & Kim, E. G. Myosin II directly binds and inhibits Dbl family guanine nucleotide exchange factors: a possible link to Rho family GTPases. J. Cell Biol. 190, 663–674 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Premkumar, L. et al. Structural basis of membrane targeting by the Dock180 family of Rho family guanine exchange factors (Rho-GEFs). J. Biol. Chem. 285, 13211–13222 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Kunisaki, Y. et al. DOCK2 is a Rac activator that regulates motility and polarity during neutrophil chemotaxis. J. Cell Biol. 174, 647–652 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Kanai, A. et al. Identification of DOCK4 and its splicing variant as PIP3 binding proteins. IUBMB Life 60, 467–472 (2008).

    Article  CAS  PubMed  Google Scholar 

  89. Fritsch, R. et al. RAS and RHO families of GTPases directly regulate distinct phosphoinositide 3-kinase isoforms. Cell 153, 1050–1063 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Zheng, Y., Bagrodia, S. & Cerione, R. A. Activation of phosphoinositide 3-kinase activity by Cdc42Hs binding to p85. J. Biol. Chem. 269, 18727–18730 (1994).

    Article  CAS  PubMed  Google Scholar 

  91. Goryachev, A. B. & Leda, M. Many roads to symmetry breaking: molecular mechanisms and theoretical models of yeast cell polarity. Mol. Biol. Cell 28, 370–380 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Cherfils, J. & Zeghouf, M. Regulation of small GTPases by GEFs, GAPs, and GDIs. Physiol. Rev. 93, 269–309 (2013).

    Article  CAS  PubMed  Google Scholar 

  93. Hennig, A., Markwart, R., Esparza-Franco, M. A., Ladds, G. & Rubio, I. Ras activation revisited: role of GEF and GAP systems. Biol. Chem. 396, 831–848 (2015).

    Article  CAS  PubMed  Google Scholar 

  94. Arkowitz, R. A. & Bassilana, M. Polarized growth in fungi: symmetry breaking and hyphal formation. Semin. Cell Dev. Biol. 22, 806–815 (2011).

    Article  CAS  PubMed  Google Scholar 

  95. Martin, S. G. & Arkowitz, R. A. Cell polarization in budding and fission yeasts. FEMS Microbiol. Rev. 38, 228–253 (2014).

    Article  CAS  PubMed  Google Scholar 

  96. Bi, E. & Park, H. O. Cell polarization and cytokinesis in budding yeast. Genetics 191, 347–387 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Chiou, J. G., Balasubramanian, M. K. & Lew, D. J. Cell polarity in yeast. Annu. Rev. Cell Dev. Biol. 33, 77–101 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Richman, T. J., Sawyer, M. M. & Johnson, D. I. Saccharomyces cerevisiae Cdc42p localizes to cellular membranes and clusters at sites of polarized growth. Eukaryot. Cell 1, 458–468 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Adams, A. E., Johnson, D. I., Longnecker, R. M., Sloat, B. F. & Pringle, J. R. CDC42 and CDC43, two additional genes involved in budding and the establishment of cell polarity in the yeast Saccharomyces cerevisiae. J. Cell Biol. 111, 131–142 (1990).

    Article  CAS  PubMed  Google Scholar 

  100. Johnson, D. I. & Pringle, J. R. Molecular characterization of CDC42, a Saccharomyces cerevisiae gene involved in the development of cell polarity. J. Cell Biol. 111, 143–152 (1990).

    Article  CAS  PubMed  Google Scholar 

  101. Wedlich-Soldner, R., Wai, S. C., Schmidt, T. & Li, R. Robust cell polarity is a dynamic state established by coupling transport and GTPase signaling. J. Cell Biol. 166, 889–900 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Tong, Z. et al. Adjacent positioning of cellular structures enabled by a Cdc42 GTPase-activating protein-mediated zone of inhibition. J. Cell Biol. 179, 1375–1384 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Okada, S., Lee, M. E., Bi, E. & Park, H. O. Probing Cdc42 polarization dynamics in budding yeast using a biosensor. Methods Enzymol. 589, 171–190 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Lichius, A. et al. CDC-42 and RAC-1 regulate opposite chemotropisms in Neurospora crassa. J. Cell Sci. 127, 1953–1965 (2014).

    Article  CAS  PubMed  Google Scholar 

  105. Okada, S. et al. Daughter cell identity emerges from the interplay of Cdc42, septins, and exocytosis. Dev. Cell 26, 148–161 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Caudron, F. & Barral, Y. Septins and the lateral compartmentalization of eukaryotic membranes. Dev. Cell 16, 493–506 (2009).

    Article  CAS  PubMed  Google Scholar 

  107. Virag, A., Lee, M. P., Si, H. & Harris, S. D. Regulation of hyphal morphogenesis by Cdc42 and Rac1 homologues in Aspergillus nidulans. Mol. Microbiol. 66, 1579–1596 (2007).

    Article  CAS  PubMed  Google Scholar 

  108. Böhmer, C., Ripp, C. & Bölker, M. The germinal centre kinase Don3 triggers the dynamic rearrangement of higher-order septin structures during cytokinesis in Ustilago maydis. Mol. Microbiol. 74, 1484–1496 (2009).

    Article  PubMed  Google Scholar 

  109. Kayano, Y., Tanaka, A. & Takemoto, D. Two closely related Rho GTPases, Cdc42 and RacA, of the en-dophytic fungus Epichloë festucae have contrasting roles for ROS production and symbiotic infection synchronized with the host plant. PLoS Pathog. 14, e1006840 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  110. Pan, X., Pérez-Henríquez, P., Van Norman, J. M. & Yang, Z. Membrane nanodomains: dynamic nanobuilding blocks of polarized cell growth. Plant. Physiol. 193, 83–97 (2023).

    Article  CAS  PubMed  Google Scholar 

  111. Li, E. et al. Signaling network controlling ROP-mediated tip growth in Arabidopsis and beyond. Plant. Commun. 4, 100451 (2023).

    Article  PubMed  Google Scholar 

  112. Ou, H. & Yi, P. ROP GTPase-dependent polarity establishment during tip growth in plants. N. phytol. 236, 49–57 (2022).

    Article  CAS  Google Scholar 

  113. Mulvey, H. & Dolan, L. RHO GTPase of plants regulates polarized cell growth and cell division orientation during morphogenesis. Curr. Biol. 33, 2897–2911.e6 (2023).

    Article  CAS  PubMed  Google Scholar 

  114. Drubin, D. G. Development of cell polarity in budding yeast. Cell 65, 1093–1096 (1991).

    Article  CAS  PubMed  Google Scholar 

  115. Park, H. O. & Bi, E. Central roles of small GTPases in the development of cell polarity in yeast and beyond. Microbiol. Mol. Biol. Rev. 71, 48–96 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Ayscough, K. R. et al. High rates of actin filament turnover in budding yeast and roles for actin in establishment and maintenance of cell polarity revealed using the actin inhibitor latrunculin-A. J. Cell Biol. 137, 399–416 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Butty, A. C., Pryciak, P. M., Huang, L. S., Herskowitz, I. & Peter, M. The role of Far1p in linking the heterotrimeric G protein to polarity establishment proteins during yeast mating. Science 282, 1511–1516 (1998).

    Article  CAS  PubMed  Google Scholar 

  118. Li, R. & Bowerman, B. Symmetry breaking in biology. Cold Spring Harb. Perspect. Biol. 2, a003475 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  119. Irazoqui, J. E., Gladfelter, A. S. & Lew, D. J. Scaffold-mediated symmetry breaking by Cdc42p. Nat. Cell Biol. 5, 1062–1070 (2003).

    Article  CAS  PubMed  Google Scholar 

  120. Kozubowski, L. et al. Symmetry-breaking polarization driven by a Cdc42p GEF–PAK complex. Curr. Biol. 18, 1719–1726 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Woods, B., Kuo, C. C., Wu, C. F., Zyla, T. R. & Lew, D. J. Polarity establishment requires localized activation of Cdc42. J. Cell Biol. 211, 19–26 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Witte, K., Strickland, D. & Glotzer, M. Cell cycle entry triggers a switch between two modes of Cdc42 activation during yeast polarization. eLife 6, e26722 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  123. Chang, E. C. et al. Cooperative interaction of S. pombe proteins required for mating and morphogenesis. Cell 79, 131–141 (1994).

    Article  CAS  PubMed  Google Scholar 

  124. Lamas, I., Merlini, L., Vještica, A., Vincenzetti, V. & Martin, S. G. Optogenetics reveals Cdc42 local activation by scaffold-mediated positive feedback and Ras GTPase. PLoS Biol. 18, e3000600 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  125. Altschuler, S. J., Angenent, S. B., Wang, Y. & Wu, L. F. On the spontaneous emergence of cell polarity. Nature 454, 886–889 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Wedlich-Soldner, R., Altschuler, S., Wu, L. & Li, R. Spontaneous cell polarization through actomyosin-based delivery of the Cdc42 GTPase. Science 299, 1231–1235 (2003).

    Article  CAS  PubMed  Google Scholar 

  127. Wu, C. F., Savage, N. S. & Lew, D. J. Interaction between bud-site selection and polarity-establishment machineries in budding yeast. Philos. Trans. R. Soc. Lond. B Biol. Sci. 368, 20130006 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  128. Wu, C. F. et al. Role of competition between polarity sites in establishing a unique front. eLife 4, e11611 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  129. Otsuji, M. et al. A mass conserved reaction-diffusion system captures properties of cell polarity. PLoS Comput. Biol. 3, e108 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  130. Chiou, J. G. et al. Principles that govern competition or co-existence in Rho-GTPase driven polarization. PLoS Comput. Biol. 14, e1006095 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  131. Brauns, F., Halatek, J. & Frey, E. Phase-space geometry of mass-conserving reaction-diffusion dynamics. Phys. Rev. X 10, 041036 (2020).

    CAS  Google Scholar 

  132. Verschueren, N. & Champneys, A. A model for cell polarization without mass conservation. SIAM J. Appl. Dyn. Syst. 16, 1797–1830 (2017).

    Article  Google Scholar 

  133. Goryachev, A. B. & Leda, M. Compete or coexist? Why the same mechanisms of symmetry breaking can yield distinct outcomes. Cells 9, 2011 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Mori, Y., Jilkine, A. & Edelstein-Keshet, L. Wave-pinning and cell polarity from a bistable reaction-diffusion system. Biophys. J. 94, 3684–3697 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Smith, S. E. et al. Independence of symmetry breaking on Bem1-mediated autocatalytic activation of Cdc42. J. Cell Biol. 202, 1091–1106 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Klunder, B., Freisinger, T., Wedlich-Soldner, R. & Frey, E. GDI-mediated cell polarization in yeast provides precise spatial and temporal control of Cdc42 signaling. PLoS Comput. Biol. 9, e1003396 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  137. Freisinger, T. et al. Establishment of a robust single axis of cell polarity by coupling multiple positive feedback loops. Nat. Commun. 4, 1807 (2013).

    Article  PubMed  Google Scholar 

  138. Jose, M., Tollis, S., Nair, D., Sibarita, J. B. & McCusker, D. Robust polarity establishment occurs via an endocytosis-based cortical corralling mechanism. J. Cell Biol. 200, 407–418 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Giese, W., Eigel, M., Westerheide, S., Engwer, C. & Klipp, E. Influence of cell shape, inhomogeneities and diffusion barriers in cell polarization models. Phys. Biol. 12, 066014 (2015).

    Article  PubMed  Google Scholar 

  140. Lee, M. E., Lo, W. C., Miller, K. E., Chou, C. S. & Park, H. O. Regulation of Cdc42 polarization by the Rsr1 GTPase and Rga1, a Cdc42 GTPase-activating protein, in budding yeast. J. Cell Sci. 128, 2106–2117 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Lo, W. C., Lee, M. E., Narayan, M., Chou, C. S. & Park, H. O. Polarization of diploid daughter cells directed by spatial cues and GTP hydrolysis of Cdc42 budding yeast. PLoS ONE 8, e56665 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Bonazzi, D. et al. Actin-based transport adapts polarity domain size to local cellular curvature. Curr. Biol. 25, 2677–2683 (2015).

    Article  CAS  PubMed  Google Scholar 

  143. Bonazzi, D. et al. Symmetry breaking in spore germination relies on an interplay between polar cap stability and spore wall mechanics. Dev. Cell 28, 534–546 (2014).

    Article  CAS  PubMed  Google Scholar 

  144. Daalman, W. K., Sweep, E. & Laan, L. A tractable physical model for the yeast polarity predicts epistasis and fitness. Philos. Trans. R. Soc. Lond. B Biol. Sci. 378, 20220044 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Kuo, C. C. et al. Inhibitory GEF phosphorylation provides negative feedback in the yeast polarity circuit. Curr. Biol. 24, 753–759 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Dyer, J. M. et al. Tracking shallow chemical gradients by actin-driven wandering of the polarization site. Curr. Biol. 23, 32–41 (2013).

    Article  CAS  PubMed  Google Scholar 

  147. Howell, A. S. et al. Negative feedback enhances robustness in the yeast polarity establishment circuit. Cell 149, 322–333 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Khalili, B., Merlini, L., Vincenzetti, V., Martin, S. G. & Vavylonis, D. Exploration and stabilization of Ras1 mating zone: a mechanism with positive and negative feedbacks. PLoS Comput. Biol. 14, e1006317 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  149. Ghose, D. & Lew, D. Mechanistic insights into actin-driven polarity site movement in yeast. Mol. Biol. Cell 31, 1085–1102 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Layton, A. T. et al. Modeling vesicle traffic reveals unexpected consequences for Cdc42p-mediated polarity establishment. Curr. Biol. 21, 184–194 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Watson, L. J., Rossi, G. & Brennwald, P. Quantitative analysis of membrane trafficking in regulation of Cdc42 polarity. Traffic 15, 1330–1343 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Gerganova, V. et al. Cell patterning by secretion-induced plasma membrane flows. Sci. Adv. 7, eabg6718 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Khalili, B., Lovelace, H. D., Rutkowski, D. M., Holz, D. & Vavylonis, D. Fission yeast polarization: modeling Cdc42 oscillations, symmetry breaking, and zones of activation and inhibition. Cells 9, 1769 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Pino, M. R. et al. Cdc42 GTPase-activating proteins (GAPs) regulate generational inheritance of cell polarity and cell shape in fission yeast. Mol. Biol. Cell 32, ar14 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Coravos, J. S., Mason, F. M. & Martin, A. C. Actomyosin pulsing in tissue integrity maintenance during morphogenesis. Trends Cell Biol. 27, 276–283 (2017).

    Article  CAS  PubMed  Google Scholar 

  156. Munjal, A., Philippe, J. M., Munro, E. & Lecuit, T. A self-organized biomechanical network drives shape changes during tissue morphogenesis. Nature 524, 351–355 (2015).

    Article  CAS  PubMed  Google Scholar 

  157. Munjal, A. & Lecuit, T. Actomyosin networks and tissue morphogenesis. Development 141, 1789–1793 (2014).

    Article  CAS  PubMed  Google Scholar 

  158. Coravos, J. S. & Martin, A. C. Apical sarcomere-like actomyosin contracts nonmuscle Drosophila epithelial cells. Dev. Cell 39, 346–358 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Kim, H. Y. & Davidson, L. A. Punctuated actin contractions during convergent extension and their permissive regulation by the non-canonical Wnt-signaling pathway. J. Cell Sci. 124, 635–646 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Munro, E., Nance, J. & Priess, J. R. Cortical flows powered by asymmetrical contraction transport PAR proteins to establish and maintain anterior-posterior polarity in the early C. elegans embryo. Dev. Cell 7, 413–424 (2004).

    Article  CAS  PubMed  Google Scholar 

  161. Costache, V. et al. Rapid assembly of a polar network architecture drives efficient actomyosin contractility. Cell Rep. 39, 110868 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Mason, F. M., Tworoger, M. & Martin, A. C. Apical domain polarization localizes actin–myosin activity to drive ratchet-like apical constriction. Nat. Cell Biol. 15, 926–936 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Nishikawa, M., Naganathan, S. R., Jülicher, F. & Grill, S. W. Controlling contractile instabilities in the actomyosin cortex. eLife 6, e19595 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  164. Schmutz, C., Stevens, J. & Spang, A. Functions of the novel RhoGAP proteins RGA-3 and RGA-4 in the germ line and in the early embryo of C. elegans. Development 134, 3495–3505 (2007).

    Article  CAS  PubMed  Google Scholar 

  165. Baird, M. A. et al. Local pulsatile contractions are an intrinsic property of the myosin 2A motor in the cortical cytoskeleton of adherent cells. Mol. Biol. Cell 28, 240–251 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Beach, J. R. et al. Actin dynamics and competition for myosin monomer govern the sequential amplification of myosin filaments. Nat. Cell Biol. 19, 85–93 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Lehtimäki, J. I., Rajakylä, E. K., Tojkander, S. & Lappalainen, P. Generation of stress fibers through myosin-driven reorganization of the actin cortex. eLife 10, e60710 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  168. Kumari, A. et al. Actomyosin-driven force patterning controls endocytosis at the immune synapse. Nat. Commun. 10, 2870 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  169. Kamps, D. et al. Optogenetic tuning reveals Rho amplification-dependent dynamics of a cell contraction signal network. Cell Rep. 33, 108467 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Chen, X., Venkatachalapathy, M., Dehmelt, L. & Wu, Y. W. Multidirectional activity control of cellular processes by a versatile chemo-optogenetic approach. Angew. Chem. Int. Ed. Engl. 57, 11993–11997 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Beta, C., Edelstein-Keshet, L., Gov, N. & Yochelis, A. From actin waves to mechanism and back: how theory aids biological understanding. eLife 12, e87181 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  172. Sokac, A. M. & Bement, W. M. Kiss-and-coat and compartment mixing: coupling exocytosis to signal generation and local actin assembly. Mol. Biol. Cell 17, 1495–1502 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Nemoto, T., Kojima, T., Oshima, A., Bito, H. & Kasai, H. Stabilization of exocytosis by dynamic F-actin coating of zymogen granules in pancreatic acini. J. Biol. Chem. 279, 37544–37550 (2004).

    Article  CAS  PubMed  Google Scholar 

  174. Rousso, T., Schejter, E. D. & Shilo, B. Z. Orchestrated content release from Drosophila glue-protein vesicles by a contractile actomyosin network. Nat. Cell Biol. 18, 181–190 (2016).

    Article  CAS  PubMed  Google Scholar 

  175. Ma, W. et al. Arp2/3 nucleates F-actin coating of fusing insulin granules in pancreatic β cells to control insulin secretion. J. Cell Sci. 133, jcs236794 (2020).

    Article  CAS  PubMed  Google Scholar 

  176. Miklavc, P., Wittekindt, O. H., Felder, E. & Dietl, P. Ca2+-dependent actin coating of lamellar bodies after exocytotic fusion: a prerequisite for content release or kiss-and-run. Ann. N. Y. Acad. Sci. 1152, 43–52 (2009).

    Article  CAS  PubMed  Google Scholar 

  177. Nightingale, T. D. et al. Actomyosin II contractility expels von Willebrand factor from Weibel–Palade bodies during exocytosis. J. Cell Biol. 194, 613–629 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Yu, H. Y. & Bement, W. M. Control of local actin assembly by membrane fusion-dependent compartment mixing. Nat. Cell Biol. 9, 149–159 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Yu, H. Y. & Bement, W. M. Multiple myosins are required to coordinate actin assembly with coat compression during compensatory endocytosis. Mol. Biol. Cell 18, 4096–4105 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. Miklavc, P. et al. Actin coating and compression of fused secretory vesicles are essential for surfactant secretion—a role for Rho, formins and myosin II. J. Cell Sci. 125, 2765–2774 (2012).

    CAS  PubMed  Google Scholar 

  181. Tran, D. T., Masedunskas, A., Weigert, R. & Ten Hagen, K. G. Arp2/3-mediated F-actin formation controls regulated exocytosis in vivo. Nat. Commun. 6, 10098 (2015).

    Article  PubMed  Google Scholar 

  182. Mietkowska, M., Schuberth, C., Wedlich-Söldner, R. & Gerke, V. Actin dynamics during Ca2+-dependent exocytosis of endothelial Weibel–Palade bodies. Biochim. Biophys. Acta Mol. Cell Res. 1866, 1218–1229 (2019).

    Article  CAS  PubMed  Google Scholar 

  183. Sokac, A. M., Schietroma, C., Gundersen, C. B. & Bement, W. M. Myosin-1c couples assembling actin to membranes to drive compensatory endocytosis. Dev. Cell 11, 629–640 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Kamalesh, K. et al. Exocytosis by vesicle crumpling maintains apical membrane homeostasis during exocrine secretion. Dev. Cell 56, 1603–1616.e6 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  185. Miklavc, P. et al. Actin depolymerisation and crosslinking join forces with myosin II to contract actin coats on fused secretory vesicles. J. Cell Sci. 128, 1193–1203 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  186. Kono, K., Saeki, Y., Yoshida, S., Tanaka, K. & Pellman, D. Proteasomal degradation resolves competition between cell polarization and cellular wound healing. Cell 150, 151–164 (2012).

    Article  CAS  PubMed  Google Scholar 

  187. Xu, J. et al. Redox-sensitive CDC-42 clustering promotes wound closure in C. elegans. Cell Rep. 37, 110040 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  188. Horn, A. et al. Mitochondrial redox signaling enables repair of injured skeletal muscle cells. Sci. Signal. 10, eaaj1978 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  189. Moe, A. M., Golding, A. E. & Bement, W. M. Cell healing: calcium, repair and regeneration. Semin. Cell Dev. Biol. 45, 18–23 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  190. Verboon, J. M. & Parkhurst, S. M. Rho family GTPases bring a familiar ring to cell wound repair. Small GTPases 6, 1–7 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  191. Golding, A. E., Visco, I., Bieling, P. & Bement, W. M. Extraction of active RhoGTPases by RhoGDI regulates spatiotemporal patterning of RhoGTPases. eLife 8, e50471 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  192. Vaughan, E. M., Miller, A. L., Yu, H. Y. & Bement, W. M. Control of local Rho GTPase crosstalk by Abr. Curr. Biol. 21, 270–277 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  193. Nakamura, M., Verboon, J. M. & Parkhurst, S. M. Prepatterning by RhoGEFs governs Rho GTPase spatiotemporal dynamics during wound repair. J. Cell Biol. 216, 3959–3969 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  194. Mandato, C. A. & Bement, W. M. Contraction and polymerization cooperate to assemble and close actomyosin rings around Xenopus oocyte wounds. J. Cell Biol. 154, 785–797 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  195. Hui, J., Nakamura, M., Dubrulle, J. & Parkhurst, S. M. Coordinated efforts of different actin filament populations are needed for optimal cell wound repair. Mol. Biol. Cell 34, ar15 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  196. Abreu-Blanco, M. T., Verboon, J. M. & Parkhurst, S. M. Cell wound repair in Drosophila occurs through three distinct phases of membrane and cytoskeletal remodeling. J. Cell Biol. 193, 455–464 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  197. Holmes, W. R., Golding, A. E., Bement, W. M. & Edelstein-Keshet, L. A mathematical model of GTPase pattern formation during single-cell wound repair. Interface Focus. 6, 20160032 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  198. Simon, C. M., Vaughan, E. M., Bement, W. M. & Edelstein-Keshet, L. Pattern formation of Rho GTPases in single cell wound healing. Mol. Biol. Cell 24, 421–432 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  199. Chuang, T. H. et al. Abr and Bcr are multifunctional regulators of the Rho GTP-binding protein family. Proc. Natl Acad. Sci. USA 92, 10282–10286 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  200. Davenport, N. R., Sonnemann, K. J., Eliceiri, K. W. & Bement, W. M. Membrane dynamics during cellular wound repair. Mol. Biol. Cell 27, 2272–2285 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  201. Vaughan, E. M. et al. Lipid domain-dependent regulation of single-cell wound repair. Mol. Biol. Cell 25, 1867–1876 (2014).

  202. Moe, A. et al. Cross-talk-dependent cortical patterning of Rho GTPases during cell repair. Mol. Biol. Cell 32, 1417–1432 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  203. Yüce, O., Piekny, A. & Glotzer, M. An ECT2–centralspindlin complex regulates the localization and function of RhoA. J. Cell Biol. 170, 571–582 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  204. Wagner, E. & Glotzer, M. Local RhoA activation induces cytokinetic furrows independent of spindle position and cell cycle stage. J. Cell Biol. 213, 641–649 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  205. Bastos, R. N., Penate, X., Bates, M., Hammond, D. & Barr, F. A. CYK4 inhibits Rac1-dependent PAK1 and ARHGEF7 effector pathways during cytokinesis. J. Cell Biol. 198, 865–880 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  206. Su, K. C., Takaki, T. & Petronczki, M. Targeting of the RhoGEF Ect2 to the equatorial membrane controls cleavage furrow formation during cytokinesis. Dev. Cell 21, 1104–1115 (2011).

    Article  CAS  PubMed  Google Scholar 

  207. Nishimura, Y. & Yonemura, S. Centralspindlin regulates ECT2 and RhoA accumulation at the equatorial cortex during cytokinesis. J. Cell Sci. 119, 104–114 (2006).

    Article  CAS  PubMed  Google Scholar 

  208. Jordan, S. N. & Canman, J. C. Rho GTPases in animal cell cytokinesis: an occupation by the one percent. Cytoskeleton 69, 919–930 (2012).

    Article  CAS  PubMed  Google Scholar 

  209. Zhuravlev, Y. et al. CYK-4 regulates Rac, but not Rho, during cytokinesis. Mol. Biol. Cell 28, 1258–1270 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  210. Canman, J. C. et al. Inhibition of Rac by the GAP activity of centralspindlin is essential for cytokinesis. Science 322, 1543–1546 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  211. Zhang, D. & Glotzer, M. The RhoGAP activity of CYK-4/MgcRacGAP functions non-canonically by promoting RhoA activation during cytokinesis. eLife 4, e08898 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  212. Loria, A., Longhini, K. M. & Glotzer, M. The RhoGAP domain of CYK-4 has an essential role in RhoA activation. Curr. Biol. 22, 213–219 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  213. Swider, Z. T. et al. Cell cycle and developmental control of cortical excitability in Xenopus laevis. Mol. Biol. Cell 33, ar73 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  214. Michaud, A. et al. A versatile cortical pattern-forming circuit based on Rho, F-actin, Ect2, and RGA-3/4. J. Cell Biol. 221, e202203017 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  215. Zanin, E. et al. A conserved RhoGAP limits M phase contractility and coordinates with microtubule asters to confine RhoA during cytokinesis. Dev. Cell 26, 496–510 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  216. Bell, K. R. et al. Novel cytokinetic ring components drive negative feedback in cortical contractility. Mol. Biol. Cell 31, 1623–1636 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  217. Krendel, M., Zenke, F. T. & Bokoch, G. M. Nucleotide exchange factor GEF-H1 mediates cross-talk between microtubules and the actin cytoskeleton. Nat. Cell Biol. 4, 294–301 (2002).

    Article  CAS  PubMed  Google Scholar 

  218. Tong, C. S., Xu, X. J. & Wu, M. Periodicity, mixed-mode oscillations, and multiple timescale in a phosphoinositide–Rho GTPase network. Cell Rep. 42, 112857 (2023).

    Article  CAS  PubMed  Google Scholar 

  219. Scott, D. W., Tolbert, C. E. & Burridge, K. Tension on JAM-A activates RhoA via GEF-H1 and p115 RhoGEF. Mol. Biol. Cell 27, 1420–1430 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  220. Scholze, M. J. et al. PI(4,5)P(2) forms dynamic cortical structures and directs actin distribution as well as polarity in Caenorhabditis elegans embryos. Development 145, dev164988 (2018).

    Article  PubMed  Google Scholar 

  221. Reyes, C. C. et al. Anillin regulates cell–cell junction integrity by organizing junctional accumulation of Rho-GTP and actomyosin. Curr. Biol. 24, 1263–1270 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  222. Terry, S. J. et al. Spatially restricted activation of RhoA signalling at epithelial junctions by p114RhoGEF drives junction formation and morphogenesis. Nat. Cell Biol. 13, 159–166 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  223. Ratheesh, A., Priya, R. & Yap, A. S. Coordinating Rho and Rac: the regulation of Rho GTPase signaling and cadherin junctions. Prog. Mol. Biol. Transl. Sci. 116, 49–68 (2013).

    Article  CAS  PubMed  Google Scholar 

  224. Varadarajan, S., Stephenson, R. E. & Miller, A. L. Multiscale dynamics of tight junction remodeling. J. Cell Sci. 132, jcs229286 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  225. Citi, S., Guerrera, D., Spadaro, D. & Shah, J. Epithelial junctions and Rho family GTPases: the zonular signalosome. Small GTPases 5, 1–15 (2014).

    Article  PubMed  Google Scholar 

  226. Arnold, T. R., Stephenson, R. E. & Miller, A. L. Rho GTPases and actomyosin: partners in regulating epithelial cell–cell junction structure and function. Exp. Cell Res. 358, 20–30 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  227. Ratheesh, A. et al. Centralspindlin and α-catenin regulate Rho signalling at the epithelial zonula adherens. Nat. Cell Biol. 14, 818–828 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  228. Breznau, E. B., Semack, A. C., Higashi, T. & Miller, A. L. MgcRacGAP restricts active RhoA at the cytokinetic furrow and both RhoA and Rac1 at cell–cell junctions in epithelial cells. Mol. Biol. Cell 26, 2439–2455 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  229. Arnold, T. R. et al. Anillin regulates epithelial cell mechanics by structuring the medial–apical actomyosin network. eLife 8, e39062 (2019).

    Article  Google Scholar 

  230. Priya, R. et al. Bistable front dynamics in a contractile medium: travelling wave fronts and cortical advection define stable zones of RhoA signaling at epithelial adherens junctions. PLoS Comput. Biol. 13, e1005411 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  231. Stephenson, R. E. et al. Rho flares repair local tight junction leaks. Dev. Cell 48, 445–459.e5 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  232. Varadarajan, S. et al. Mechanosensitive calcium flashes promote sustained RhoA activation during tight junction remodeling. J. Cell Biol. 221, e202102107 (2022).

    Article  Google Scholar 

  233. Chumki, S. A., van den Goor, L. M., Hall, B. N. & Miller, A. L. p115RhoGEF activates RhoA to support tight junction maintenance and remodeling. Mol. Biol. Cell 33, ar136 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  234. Weiner, O. D., Marganski, W. A., Wu, L. F., Altschuler, S. J. & Kirschner, M. W. An actin-based wave generator organizes cell motility. PLoS Biol. 5, e221 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  235. Sonnemann, K. J. & Bement, W. M. Wound repair: toward understanding and integration of single-cell and multicellular wound responses. Annu. Rev. Cell Dev. Biol. 27, 237–263 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  236. Yao, B., Donoughe, S., Michaux, J. & Munro, E. Modulating RhoA effectors induces transitions to oscillatory and more wavelike RhoA dynamics in Caenorhabditis elegans zygotes. Mol. Biol. Cell 33, ar58 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  237. Xie, S. & Martin, A. C. Intracellular signalling and intercellular coupling coordinate heterogeneous contractile events to facilitate tissue folding. Nat. Commun. 6, 7161 (2015).

    Article  PubMed  Google Scholar 

  238. Zulueta-Coarasa, T. & Fernandez-Gonzalez, R. Dynamic force patterns promote collective cell movements during embryonic wound repair. Nat. Phys. 14, 750–758 (2018).

    Article  CAS  Google Scholar 

  239. Cavanaugh, K. E., Chmiel, T. A. & Gardel, M. L. Caveolae spelunking: exploring a new modality in tensional homeostasis. Dev. Cell 54, 3–5 (2020).

    Article  CAS  PubMed  Google Scholar 

  240. Mak, M., Zaman, M. H., Kamm, R. D. & Kim, T. Interplay of active processes modulates tension and drives phase transition in self-renewing, motor-driven cytoskeletal networks. Nat. Commun. 7, 10323 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  241. Su, K. C., Bement, W. M., Petronczki, M. & von Dassow, G. An astral simulacrum of the central spindle accounts for normal, spindle-less, and anucleate cytokinesis in echinoderm embryos. Mol. Biol. Cell 25, 4049–4062 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  242. Poirier, M. B., Fiorino, C., Rajasekar, T. K. & Harrison, R. E. F-Actin flashes on phagosomes mechanically deform contents for efficient digestion in macrophages. J. Cell Sci. 133, jcs239384 (2020).

    Article  CAS  PubMed  Google Scholar 

  243. Herron, J. C. et al. Spatial models of pattern formation during phagocytosis. PLoS Comput. Biol. 18, e1010092 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  244. Kreider-Letterman, G. et al. ARHGAP17 regulates the spatiotemporal activity of Cdc42 at invadopodia. J. Cell Biol. 222, e202207020 (2023).

    Article  CAS  PubMed  Google Scholar 

  245. Reinhard, N. R. et al. Spatiotemporal analysis of RhoA/B/C activation in primary human endothelial cells. Sci. Rep. 6, 25502 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  246. Case, L. B. & Waterman, C. M. Adhesive F-actin waves: a novel integrin-mediated adhesion complex coupled to ventral actin polymerization. PLoS ONE 6, e26631 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  247. van Loon, A. P., Erofeev, I. S., Goryachev, A. B. & Sagasti, A. Stochastic contraction of myosin minifilaments drives evolution of microridge protrusion patterns in epithelial cells. Mol. Biol. Cell 32, 1501–1513 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  248. van Loon, A. P., Erofeev, I. S., Maryshev, I. V., Goryachev, A. B. & Sagasti, A. Cortical contraction drives the 3D patterning of epithelial cell surfaces. J. Cell Biol. 219, e201904144 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  249. Sternberg, H. et al. Formation of self-organizing functionally distinct Rho of plants domains involves a reduced mobile population. Plant. Physiol. 187, 2485–2508 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  250. Fritz, R. D. & Pertz, O. The dynamics of spatio-temporal Rho GTPase signaling: formation of signaling patterns. F1000Res 5, https://doi.org/10.12688/f1000research.7370.1 (2016).

  251. Bolado-Carrancio, A. et al. Periodic propagating waves coordinate RhoGTPase network dynamics at the leading and trailing edges during cell migration. eLife 9, e58165 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  252. Yang, H. W., Collins, S. R. & Meyer, T. Locally excitable Cdc42 signals steer cells during chemotaxis. Nat. Cell Biol. 18, 191–201 (2016).

    Article  CAS  PubMed  Google Scholar 

  253. Martin, K. et al. Spatio-temporal co-ordination of RhoA, Rac1 and Cdc42 activation during prototypical edge protrusion and retraction dynamics. Sci. Rep. 6, 21901 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  254. Huang, C. H., Tang, M., Shi, C., Iglesias, P. A. & Devreotes, P. N. An excitable signal integrator couples to an idling cytoskeletal oscillator to drive cell migration. Nat. Cell Biol. 15, 1307–1316 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  255. Mahlandt, E. K., Kreider-Letterman, G., Chertkova, A. O., Garcia-Mata, R. & Goedhart, J. Cell-based optimization and characterization of genetically encoded location-based biosensors for Cdc42 or Rac activity. J. Cell Sci. 136, jcs260802 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  256. Mahlandt, E. K. et al. Visualizing endogenous Rho activity with an improved localization-based, genetically encoded biosensor. J. Cell Sci. 134, jcs258823 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  257. Azoitei, M. L. et al. Spatiotemporal dynamics of GEF-H1 activation controlled by microtubule- and Src-mediated pathways. J. Cell Biol. 218, 3077–3097 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  258. Ichikawa, T., Stuckenholz, C. & Davidson, L. A. Non-junctional role of Cadherin3 in cell migration and contact inhibition of locomotion via domain-dependent, opposing regulation of Rac1. Sci. Rep. 10, 17326 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  259. Floerchinger, A. et al. Optimizing metastatic-cascade-dependent Rac1 targeting in breast cancer: guidance using optical window intravital FRET imaging. Cell Rep. 36, 109689 (2021).

    Article  CAS  PubMed  Google Scholar 

  260. Gupta, S. et al. Enhanced RhoA signalling stabilizes E-cadherin in migrating epithelial monolayers. J. Cell Sci. 134, jcs258767 (2021).

    Article  CAS  PubMed  Google Scholar 

  261. Nanda, S. et al. Rho GTPase activity crosstalk mediated by Arhgef11 and Arhgef12 coordinates cell protrusion-retraction cycles. Nat. Commun. 14, 8356 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  262. Patwardhan, R. et al. Cdc42 activity in the trailing edge is required for persistent directional migration of keratinocytes. Mol Biol Cell. https://doi.org/10.1091/mbc.E23-08-0318 (2024).

  263. Dada, O., Gutowski, S., Brautigam, C. A., Chen, Z. & Sternweis, P. C. Direct regulation of p190RhoGEF by activated Rho and Rac GTPases. J. Struct. Biol. 202, 13–24 (2018).

    Article  CAS  PubMed  Google Scholar 

  264. Chen, Z. et al. Activation of p115-RhoGEF requires direct association of Gα13 and the Dbl homology domain. J. Biol. Chem. 287, 25490–25500 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  265. Baird, D., Feng, Q. & Cerione, R. A. The Cool-2/α-Pix protein mediates a Cdc42–Rac signaling cascade. Curr. Biol. 15, 1–10 (2005).

    Article  CAS  PubMed  Google Scholar 

  266. Bellanger, J. M. et al. The Rac1- and RhoG-specific GEF domain of Trio targets filamin to remodel cytoskeletal actin. Nat. Cell Biol. 2, 888–892 (2000).

    Article  CAS  PubMed  Google Scholar 

  267. Kim, K., Hou, P., Gorski, J. L. & Cooper, J. A. Effect of Fgd1 on cortactin in Arp2/3 complex-mediated actin assembly. Biochemistry 43, 2422–2427 (2004).

    Article  CAS  PubMed  Google Scholar 

  268. Nayal, A. et al. Paxillin phosphorylation at Ser273 localizes a GIT1–PIX–PAK complex and regulates adhesion and protrusion dynamics. J. Cell Biol. 173, 587–589 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  269. Ten Klooster, J. P. et al. Interaction between Tiam1 and the Arp2/3 complex links activation of Rac to actin polymerization. Biochem. J. 397, 39–45 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  270. Lee, C. C., Huang, C. C. & Hsu, K. S. The phospholipid-binding protein SESTD1 negatively regulates dendritic spine density by interfering with Rac1–Trio8 signaling pathway. Sci. Rep. 5, 13250 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  271. Barrows, D., He, J. Z. & Parsons, R. PREX1 protein function is negatively regulated downstream of receptor tyrosine kinase activation by p21-activated kinases (PAKs). J. Biol. Chem. 291, 20042–20054 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  272. Fauchereau, F. et al. The RhoGAP activity of OPHN1, a new F-actin-binding protein, is negatively controlled by its amino-terminal domain. Mol. Cell. Neurosci. 23, 574–586 (2003).

    Article  CAS  PubMed  Google Scholar 

  273. Schlam, D. et al. Phosphoinositide 3-kinase enables phagocytosis of large particles by terminating actin assembly through Rac/Cdc42 GTPase-activating proteins. Nat. Commun. 6, 8623 (2015).

    Article  CAS  PubMed  Google Scholar 

  274. Michaelson, D. et al. Differential localization of Rho GTPases in live cells: regulation by hypervariable regions and RhoGDI binding. J. Cell Biol. 152, 111–126 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  275. Yonemura, S., Hirao-Minakuchi, K. & Nishimura, Y. Rho localization in cells and tissues. Exp. Cell Res. 295, 300–314 (2004).

    Article  CAS  PubMed  Google Scholar 

  276. Lu, M. S. & Drubin, D. G. Cdc42 GTPase regulates ESCRTs in nuclear envelope sealing and ER remodeling. J. Cell Biol. 219, e201910119 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  277. Boulter, E. et al. Regulation of Rho GTPase crosstalk, degradation and activity by RhoGDI1. Nat. Cell Biol. 12, 477–483 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  278. Yoshizaki, H. et al. Activity of Rho-family GTPases during cell division as visualized with FRET-based probes. J. Cell Biol. 162, 223–232 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  279. Kraynov, V. S. et al. Localized Rac activation dynamics visualized in living cells. Science 290, 333–337 (2000).

    Article  CAS  PubMed  Google Scholar 

  280. Fritz, R. D. et al. A versatile toolkit to produce sensitive FRET biosensors to visualize signaling in time and space. Sci. Signal. 6, rs12 (2013).

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors thank colleagues who generously provided unpublished images: J. Michaux and E. Munro, University of Chicago; C. Tong and M. Wu, Yale University; A. Michaud, Promega Corp.; M. Graessl, P. Nalbant and L. Dehmelt, University of Duisburg and Technical University of Dortmund; and L. Hoachlander-Hobby, University of Wisconsin–Madison. W.M.B. acknowledges funding from the National Institutes of Health (NIH RO1 GM052932) and the National Science Foundation (NSF 2132606), A.L.M. acknowledges funding from the National Institutes of Health (NIH R01 GM112794) and the National Science Foundation (NSF 1615338), and A.B.G acknowledges funding from the Biotechnology and Biological Sciences Research Council (BB/W013614/1) and the Leverhulme Trust (RPG-2020-220). To the memory of Robert K. Bement, 1932–2023: ‘Er ist geflohen, als wir ihn nicht beobachteten’.

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Authors and Affiliations

  1. Center for Quantitative Cell Imaging, Department of Integrative Biology, University of Wisconsin–Madison, Madison, WI, USA

    William M. Bement

  2. Center for Engineering Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, UK

    Andrew B. Goryachev

  3. Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, USA

    Ann L. Miller

  4. Oregon Institute of Marine Biology, Charleston, OR, USA

    George von Dassow

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Bement, W.M., Goryachev, A.B., Miller, A.L. et al. Patterning of the cell cortex by Rho GTPases. Nat Rev Mol Cell Biol 25, 290–308 (2024). https://doi.org/10.1038/s41580-023-00682-z

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