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Principles of PAR polarity in Caenorhabditis elegans embryos

Nature Reviews Molecular Cell Biology volume 14, pages 315–322 (2013)Cite this article

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Abstract

A hallmark of cell polarity in metazoans is the distribution of partitioning defective (PAR) proteins into two domains on the membrane. Domain boundaries are set by the collective integration of mechanical, biochemical and biophysical signals, and the resulting PAR domains define areas of cytosol specialization. However, the complexity of the signals acting on PAR proteins has been a barrier to uncovering the general principles of PAR polarity. We propose that physical studies, when combined with genetic data, provide new understanding of the mechanisms of polarity establishment in the Caenorhabditis elegans embryo and other organisms.

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Figure 1: Properties of PAR proteins in Caenorhabditis elegans embryos.
Figure 2: Polarization of the Caenorhabditis elegans embryo at the one-cell stage.
Figure 3: Polarizing events downstream of PAR proteins.

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References

  1. Goldstein, B. & Macara, I. G. The PAR proteins: fundamental players in animal cell polarization. Dev. Cell 13, 609–622 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Knoblich, J. A. Asymmetric cell division during animal development. Nature Rev. Mol. Cell Biol. 2, 11–20 (2001).

    Article  CAS  Google Scholar 

  3. Kemphues, K. J., Priess, J. R., Morton, D. G. & Cheng, N. S. Identification of genes required for cytoplasmic localization in early C. elegans embryos. Cell 52, 311–320 (1988).

    Article  CAS  PubMed  Google Scholar 

  4. Cowan, C. R. & Hyman, A. A. Acto-myosin reorganization and PAR polarity in C. elegans. Development 134, 1035–1043 (2007).

    Article  CAS  PubMed  Google Scholar 

  5. Gönczy, P. & Hyman, A. A. Cortical domains and the mechanisms of asymmetric cell division. Trends Cell Biol. 6, 382–387 (1996).

    Article  PubMed  Google Scholar 

  6. Schneider, S. Q. & Bowerman, B. Cell polarity and the cytoskeleton in the Caenorhabditis elegans zygote. Annu. Rev. Genet. 37, 221–249 (2003).

    Article  CAS  PubMed  Google Scholar 

  7. Beatty, A., Morton, D. & Kemphues, K. The C. elegans homolog of Drosophila Lethal giant larvae functions redundantly with PAR-2 to maintain polarity in the early embryo. Development 137, 3995–4004 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Boyd, L., Guo, S., Levitan, D., Stinchcomb, D. T. & Kemphues, K. J. PAR-2 is asymmetrically distributed and promotes association of P granules and PAR-1 with the cortex in C. elegans embryos. Development 122, 3075–3084 (1996).

    CAS  PubMed  Google Scholar 

  9. Etemad-Moghadam, B., Guo, S. & Kemphues, K. J. Asymmetrically distributed PAR-3 protein contributes to cell polarity and spindle alignment in early C. elegans embryos. Cell 83, 743–752 (1995).

    Article  CAS  PubMed  Google Scholar 

  10. Guo, S. & Kemphues, K. J. par-1, a gene required for establishing polarity in C. elegans embryos, encodes a putative Ser/Thr kinase that is asymmetrically distributed. Cell 81, 611–620 (1995).

    Article  CAS  PubMed  Google Scholar 

  11. Hoege, C. et al. LGL can partition the cortex of one-cell Caenorhabditis elegans embryos into two domains. Curr. Biol. 20, 1296–1303 (2010).

    Article  CAS  PubMed  Google Scholar 

  12. Tabuse, Y. et al. Atypical protein kinase C cooperates with PAR-3 to establish embryonic polarity in Caenorhabditis elegans. Development 125, 3607–3614 (1998).

    CAS  PubMed  Google Scholar 

  13. Watts, J. L. et al. par-6, a gene involved in the establishment of asymmetry in early C. elegans embryos, mediates the asymmetric localization of PAR-3. Development 122, 3133–3140 (1996).

    CAS  PubMed  Google Scholar 

  14. Goehring, N. W., Hoege, C., Grill, S. W. & Hyman, A. A. PAR proteins diffuse freely across the anterior-posterior boundary in polarized C. elegans embryos. J. Cell Biol. 193, 583–594 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Petrásek, Z. et al. Characterization of protein dynamics in asymmetric cell division by scanning fluorescence correlation spectroscopy. Biophys. J. 95, 5476–5486 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  16. Goehring, N. W. et al. Polarization of PAR proteins by advective triggering of a pattern-forming system. Science 334, 1137–1141 (2011).

    Article  CAS  PubMed  Google Scholar 

  17. Lippincott-Schwartz, J., Altan-Bonnet, N. & Patterson, G. H. Photobleaching and photoactivation: following protein dynamics in living cells. Nature Cell Biol. 5, S7–S14 (2003).

    Article  Google Scholar 

  18. Aceto, D., Beers, M. & Kemphues, K. J. Interaction of PAR-6 with CDC-42 is required for maintenance but not establishment of PAR asymmetry in C. elegans. Dev. Biol. 299, 386–397 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Joberty, G., Petersen, C., Gao, L. & Macara, I. G. The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42. Nature Cell Biol. 2, 531–539 (2000).

    Article  CAS  PubMed  Google Scholar 

  20. Krahn, M. P. Klopfenstein, D. R., Fischer, N. & Wodarz, A. Membrane targeting of Bazooka/PAR-3 is mediated by direct binding to phosphoinositide lipids. Curr. Biol. 20, 636–642 (2010).

    Article  CAS  PubMed  Google Scholar 

  21. Moravcevic, K. et al. Kinase associated-1 domains drive MARK/PAR1 kinases to membrane targets by binding acidic phospholipids. Cell 143, 966–977 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Motegi, F. et al. Microtubules induce self-organization of polarized PAR domains in Caenorhabditis elegans zygotes. Nature Cell Biol. 13, 1361–1367 (2011).

    Article  CAS  PubMed  Google Scholar 

  23. Panbianco, C. et al. A casein kinase 1 and PAR proteins regulate asymmetry of a PIP2 synthesis enzyme for asymmetric spindle positioning. Dev. Cell 15, 198–208 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Feng, W., Wu, H., Chan, L. N. & Zhang, M. The Par-3 NTD adopts a PB1-like structure required for Par-3 oligomerization and membrane localization. EMBO J. 26, 2786–2796 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Cuenca, A. A., Schetter, A., Aceto, D., Kemphues, K. & Seydoux, G. Polarization of the C. elegans zygote proceeds via distinct establishment and maintenance phases. Development 130, 1255–1265 (2003).

    Article  CAS  PubMed  Google Scholar 

  26. Motegi, F. & Sugimoto, A. Sequential functioning of the ECT-2 RhoGEF, RHO-1 and CDC-42 establishes cell polarity in Caenorhabditis elegans embryos. Nature Cell Biol. 8, 978–985 (2006).

    Article  CAS  PubMed  Google Scholar 

  27. Nakayama, Y. et al. Dynamin participates in the maintenance of anterior polarity in the Caenorhabditis elegans embryo. Dev. Cell 16, 889–900 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Schenk, C., Bringmann, H., Hyman, A. A. & Cowan, C. R. Cortical domain correction repositions the polarity boundary to match the cytokinesis furrow in C. elegans embryos. Development 137, 1743–1753 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Schonegg, S. CDC-42 and RHO-1 coordinate acto-myosin contractility and PAR protein localization during polarity establishment in C. elegans embryos. Development 133, 3507–3516 (2006).

    Article  CAS  PubMed  Google Scholar 

  30. Hao, Y., Boyd, L. & Seydoux, G. Stabilization of cell polarity by the C. elegans RING protein PAR-2. Dev. Cell 10, 199–208 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Goehring, N. W., Chowdhury, D., Hyman, A. A. & Grill, S. W. FRAP analysis of membrane-associated proteins: lateral diffusion and membrane-cytoplasmic exchange. Biophys. J. 99, 2443–2452 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Kondo, S. & Miura, T. Reaction-diffusion model as a framework for understanding biological pattern formation. Science 329, 1616–1620 (2010).

    Article  CAS  PubMed  Google Scholar 

  33. Betschinger, J., Mechtler, K. & Knoblich, J. A. The Par complex directs asymmetric cell division by phosphorylating the cytoskeletal protein Lgl. Nature 422, 326–330 (2003).

    Article  CAS  PubMed  Google Scholar 

  34. Yamanaka, T. et al. Mammalian Lgl forms a protein complex with PAR-6 and aPKC independently of PAR-3 to regulate epithelial cell polarity. Curr. Biol. 13, 734–743 (2003).

    Article  CAS  PubMed  Google Scholar 

  35. 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 

  36. Hird, S. N. & White, J. G. Cortical and cytoplasmic flow polarity in early embryonic cells of Caenorhabditis elegans. J. Cell Biol. 121, 1343–1355 (1993).

    Article  CAS  PubMed  Google Scholar 

  37. Cowan, C. & Hyman, A. Centrosomes direct cell polarity independently of microtubule assembly in C. elegans embryos. Nature 431, 92–96 (2004).

    Article  CAS  PubMed  Google Scholar 

  38. Decker, M. et al. Limiting amounts of centrosome material set centrosome size in C. elegans embryos. Curr. Biol. 21, 1259–1267 (2011).

    Article  CAS  PubMed  Google Scholar 

  39. Goldstein, B. & Hird, S. N. Specification of the anteroposterior axis in Caenorhabditis elegans. Development 122, 1467–1474 (1996).

    CAS  PubMed  Google Scholar 

  40. O'Connell, K. F., Maxwell, K. N. & White, J. G. The spd-2 gene is required for polarization of the anteroposterior axis and formation of the sperm asters in the Caenorhabditis elegans zygote. Dev. Biol. 222, 55–70 (2000).

    Article  CAS  PubMed  Google Scholar 

  41. Hamill, D. R., Severson, A. F., Carter, J. C. & Bowerman, B. Centrosome maturation and mitotic spindle assembly in C. elegans require SPD-5, a protein with multiple coiled-coil domains. Dev. Cell 3, 673–684 (2002).

    Article  CAS  PubMed  Google Scholar 

  42. Bienkowska, D. & Cowan, C. R. Centrosomes can initiate a polarity axis from any position within one-cell C. elegans embryos. Curr. Biol. 22, 583–589 (2012).

    Article  CAS  PubMed  Google Scholar 

  43. Fortin, S. M. et al. The PAM-1 aminopeptidase regulates centrosome positioning to ensure anterior-posterior axis specification in one-cell C. elegans embryos. Dev. Biol. 344, 992–1000 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Zonies, S., Motegi, F., Hao, Y. & Seydoux, G. Symmetry breaking and polarization of the C. elegans zygote by the polarity protein PAR-2. Development 137, 1669–1677 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. McCloskey, R. J. & Kemphues, K. J. Deubiquitylation machinery is required for embryonic polarity in Caenorhabditis elegans. PLoS Genet. 8, e1003092 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Bois, J., Jülicher, F. & Grill, S. Pattern formation in active fluids. Phys. Rev. Lett. 106, 1–4 (2011).

    Article  Google Scholar 

  47. Bray, D. & White, J. G. Cortical flow in animal cells. Science 239, 883–888 (1988).

    Article  CAS  PubMed  Google Scholar 

  48. Mayer, M., Depken, M., Bois, J. S., Jülicher, F. & Grill, S. W. Anisotropies in cortical tension reveal the physical basis of polarizing cortical flows. Nature 467, 617–621 (2010).

    Article  CAS  PubMed  Google Scholar 

  49. Cheeks, R. J. et al. C. elegans PAR proteins function by mobilizing and stabilizing asymmetrically localized protein complexes. Curr. Biol. 14, 851–862 (2004).

    Article  CAS  PubMed  Google Scholar 

  50. Gonczy, P. Mechanisms of asymmetric cell division: flies and worms pave the way. Nature Rev. Mol. Cell Biol. 9, 355–366 (2008).

    Article  Google Scholar 

  51. Schubert, C. M., Lin, R., de Vries, C. J., Plasterk, R. H. & Priess, J. R. MEX-5 and MEX-6 function to establish soma/germline asymmetry in early C. elegans embryos. Mol. Cell 5, 671–682 (2000).

    Article  CAS  PubMed  Google Scholar 

  52. Daniels, B. R., Dobrowsky, T. M., Perkins, E. M., Sun, S. X. & Wirtz, D. MEX-5 enrichment in the C. elegans early embryo mediated by differential diffusion. Development 137, 2579–2585 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Griffin, E. E., Odde, D. J. & Seydoux, G. Regulation of the MEX-5 gradient by a spatially segregated kinase/phosphatase cycle. Cell 146, 955–968 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Mello, C. C. et al. The PIE-1 protein and germline specification in C. elegans embryos. Nature 382, 710–712 (1996).

    Article  CAS  PubMed  Google Scholar 

  55. Tabara, H., Hill, R. J., Mello, C. C., Priess, J. R. & Kohara, Y. pos-1 encodes a cytoplasmic zinc-finger protein essential for germline specification in C. elegans. Development 126, 1–11 (1999).

    CAS  PubMed  Google Scholar 

  56. Hyman, A. A. & Brangwynne, C. P. Beyond stereospecificity: liquids and mesoscale organization of cytoplasm. Dev. Cell 21, 14–16 (2012).

    Article  Google Scholar 

  57. Updike, D. & Strome, S. P granule assembly and function in Caenorhabditis elegans germ cells. J. Androl. 31, 53–60 (2010).

    Article  CAS  PubMed  Google Scholar 

  58. Gallo, C. M., Wang, J. T., Motegi, F. & Seydoux, G. Cytoplasmic partitioning of P granule components is not required to specify the germline in C. elegans. Science 330, 1685–1689 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Hird, S. N., Paulsen, J. E. & Strome, S. Segregation of germ granules in living Caenorhabditis elegans embryos: cell-type-specific mechanisms for cytoplasmic localisation. Development 122, 1303–1312 (1996).

    CAS  PubMed  Google Scholar 

  60. Hanazawa, M., Yonetani, M. & Sugimoto, A. PGL proteins self associate and bind RNPs to mediate germ granule assembly in C. elegans. J. Cell Biol. 192, 929–937 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Brangwynne, C. P. et al. Germline P granules are liquid droplets that localize by controlled dissolution/condensation. Science 324, 1729–1732 (2009).

    Article  CAS  PubMed  Google Scholar 

  62. Morton, D. G. et al. The Caenorhabditis elegans par-5 gene encodes a 14-3-3 protein required for cellular asymmetry in the early embryo. Dev. Biol. 241, 47–58 (2002).

    Article  CAS  PubMed  Google Scholar 

  63. Hurov, J., Watkins, J. & Piwnicaworms, H. Atypical PKC phosphorylates PAR-1 kinases to regulate localization and activity. Curr. Biol. 14, 736–741 (2004).

    Article  CAS  PubMed  Google Scholar 

  64. Suzuki, A. et al. aPKC acts upstream of PAR-1b in both the establishment and maintenance of mammalian epithelial polarity. Curr. Biol. 14, 1425–1435 (2004).

    Article  CAS  PubMed  Google Scholar 

  65. Li, B., Kim, H., Beers, M. & Kemphues, K. Different domains of C. elegans PAR-3 are required at different times in development. Dev. Biol. 344, 745–757 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Morais-de-Sá, E. Mirouse, V. & Johnston, D. S. aPKC phosphorylation of Bazooka defines the apical/lateral border in Drosophila epithelial cells. Cell 141, 509–523 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  67. Benton, R. & Johnston, D. S. Drosophila PAR-1 and 14-3-3 inhibit Bazooka/PAR-3 to establish complementary cortical domains in polarized cells. Cell 115, 691–704 (2003).

    Article  CAS  PubMed  Google Scholar 

  68. Atwood, S. X. & Prehoda, K. E. aPKC phosphorylates Miranda to polarize fate determinants during neuroblast asymmetric cell division. Curr. Biol. 19, 723–729 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Hurd, T. W. et al. Phosphorylation-dependent binding of 14-3-3 to the polarity protein Par3 regulates cell polarity in mammalian epithelia. Curr. Biol. 13, 2082–2090 (2003).

    Article  CAS  PubMed  Google Scholar 

  70. Nishi, Y., Rogers, E., Robertson, S. M. & Lin, R. Polo kinases regulate C. elegans embryonic polarity via binding to DYRK2-primed MEX-5 and MEX-6. Development 135, 687–697 (2008).

    Article  CAS  PubMed  Google Scholar 

  71. Dahan, I., Yearim, A., Touboul, Y. & Ravid, S. The tumor suppressor Lgl1 regulates NMII-A cellular distribution and focal adhesion morphology to optimize cell migration. Mol. Biol. Cell 23, 591–601 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Strand, D. et al. The Drosophila lethal(2)giant larvae tumor suppressor protein forms homo-oligomers and is associated with nonmuscle myosin II heavy chain. J. Cell Biol. 127, 1361–1373 (1994).

    Article  CAS  PubMed  Google Scholar 

  73. Guo, S. & Kemphues, K. J. A non-muscle myosin required for embryonic polarity in Caenorhabditis elegans. Nature 382, 455–458 (1996).

    Article  CAS  PubMed  Google Scholar 

  74. Chartier, N. T. et al. PAR-4/LKB1 mobilizes nonmuscle myosin through anillin to regulate C. elegans embryonic polarization and cytokinesis. Curr. Biol. 21, 259–269 (2011).

    Article  CAS  PubMed  Google Scholar 

  75. Garrard, S. M. et al. Structure of Cdc42 in a complex with the GTPase-binding domain of the cell polarity protein, Par6. EMBO J. 22, 1125–1133 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors thank the anonymous reviewers, their colleagues in the laboratory and at the Max Planck Institute of Molecular Cell Biology for critical comments, suggestions and discussion on the manuscript. They apologize to their colleagues in the field for omitting their work due to space limitations. Work in the authors laboratory was supported by the Max-Planck-Gesellschaft (MPG) and the Deutsche Forschungsgemeinschaft (DFG).

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  1. Carsten Hoege and Anthony A. Hyman are at the Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, D-01307 Dresden, Germany.,

    Carsten Hoege & Anthony A. Hyman

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Glossary

Actomyosin

Crosslinked network of actin and non-muscle myosin filaments, which can contract by sliding along each other and which underlie the plasma membrane of the cell.

Advection

Passive transport of molecules by drag forces in liquids.

Anisotropic

Directionally dependent difference in a property of the material.

Cellular cortex

Layer on the inner side of the plasma membrane that mechanically supports the membrane. It consists of actin, non-muscle myosin (see actomyosin) and several actin-binding proteins.

Centrioles

Cylindrical structure in most cells that is typically composed of nine triplets of microtubules. Involved in the organization of the centrosome and the mitotic spindle.

Centrosome

Organelle that organizes microtubules in the cell and contains centrioles.

Effector

A product or process that operates after instructions issued by, for example, a control protein such as a kinase.

Fluorescence recovery after photobleaching

(FRAP). Microscope technique in which fluorescent molecules are studied in a defined area before and after fluorescent molecules are photobleached. The kinetics of fluorescence recovery is a readout of the mobility of the fluorescent molecules in space.

Inverse fluorescence recovery after photobleaching

(iFRAP). A special type of FRAP, in which fluorescent molecules are photobleached outside the region that is analysed.

Lateral diffusion

Two-dimensional diffusion (for example, on a surface); that is, the motion of molecules that causes flux and mixing of molecules from high to low concentrations.

P granules

Complex assembly of heterogeneous RNA and protein molecules that form spheres in the cytoplasm of the germ line, oocytes and embryos of C. elegans. Although their function is not yet solved, they seem to contribute to future germ cell fate (known as germ granules in other organisms).

Phase separation

A type of partitioning between thermodynamically similar regions of space (for example, P granules partition between two different kinds of liquids in the cytosol).

Random walks

The stochastic moving path of a molecule travelling through a medium.

Reaction–diffusion system

In biology a patterning process in which diffusive molecules (morphogens) undergo biochemical reactions (for example, phosphorylation, degradation and synthesis) and form well-defined spatial distributions.

Steady state

Dynamic equilibrium in which reactions do not change the composition of mixtures.

Tension

Pulling force that acts between solid objects.

Triggers

A cue or signal that initiates a process transforming an unpolarized cell into a polarized cell.

Viscous forces

A measure of resistance to flow. This describes the internal friction of a moving fluid (for example, fluids are more viscous than liquids).

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Hoege, C., Hyman, A. Principles of PAR polarity in Caenorhabditis elegans embryos. Nat Rev Mol Cell Biol 14, 315–322 (2013). https://doi.org/10.1038/nrm3558

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