News & Views |
Featured
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EGFR ligand shifts the role of EGFR from oncogene to tumour suppressor in EGFR-amplified glioblastoma by suppressing invasion through BIN3 upregulation
Guo et al. show that ligand-induced EGFR activation suppresses invasion by upregulating BIN3 and inhibiting DOCK7-regulated Rho GTPase activity in EGFR-amplified glioblastoma, which is in contrast to the known oncogenic role for EGFR signalling.
- Gao Guo
- , Ke Gong
- & Amyn A. Habib
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Resource |
Systems analysis of RhoGEF and RhoGAP regulatory proteins reveals spatially organized RAC1 signalling from integrin adhesions
Müller et al. provide a comprehensive resource depicting cellular substrates, localization and interacting partners of RhoGEF and RhoGAP proteins regulating the canonical Rho family of GTPases.
- Paul M. Müller
- , Juliane Rademacher
- & Oliver Rocks
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Article |
RPEL-family rhoGAPs link Rac/Cdc42 GTP loading to G-actin availability
Diring et al. identify ArhGAP12 and ArhGAP32 as RPEL proteins that bind G-actin. When bound to G-actin, ArhGAP12 cannot suppress Rac, thus coupling Rac activity to actin availability.
- Jessica Diring
- , Stephane Mouilleron
- & Richard Treisman
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Article |
Fam49/CYRI interacts with Rac1 and locally suppresses protrusions
Fort et al. identify CYRI as a conserved negative modulator of Scar–WAVE-induced lamellipodia by interacting directly with active Rac1, thereby conferring pseudopod plasticity and dynamics during motility.
- Loic Fort
- , José Miguel Batista
- & Laura M. Machesky
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Article |
Modular activation of Rho1 by GPCR signalling imparts polarized myosin II activation during morphogenesis
Lecuit and colleagues show that, depending on its interaction partner, the G-protein-coupled receptor Smog regulates myosin II activation in different locations during Drosophila morphogenesis.
- Stephen Kerridge
- , Akankshi Munjal
- & Thomas Lecuit
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Article |
Locally excitable Cdc42 signals steer cells during chemotaxis
Meyer and colleagues use fluorescent biosensors to demonstrate that chemotactic steering and cell polarization are controlled by locally excitable Cdc42 signalling.
- Hee Won Yang
- , Sean R. Collins
- & Tobias Meyer
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Article |
Feedback regulation through myosin II confers robustness on RhoA signalling at E-cadherin junctions
Yap and colleagues report that robustness of RhoA signalling at E-cadherin junctions is achieved through a feedback network that includes myosin II, ROCK1, Rnd3 and p190B RhoGAP.
- Rashmi Priya
- , Guillermo A. Gomez
- & Alpha S. Yap
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News & Views |
Merlin's wizardry guides cohesive migration
Cells often migrate in tightly connected groups with coordinated movement and polarity. The collective migration of epithelial cell sheets is now shown to be mediated by a signalling axis that involves the merlin tumour-suppressor protein, the tight-junction-associated angiomotin–Rich1 complex and the Rac1 small GTPase.
- Ansgar Zoch
- & Helen Morrison
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Article |
A molecular mechanotransduction pathway regulates collective migration of epithelial cells
Spatz and colleagues report that intercellular pulling forces between leader and follower cells in migrating epithelial sheets regulate merlin subcellular localization and the crosstalk between merlin and Rac1 to promote collective cell migration.
- Tamal Das
- , Kai Safferling
- & Joachim P. Spatz
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Article |
Myosin II controls cellular branching morphogenesis and migration in three dimensions by minimizing cell-surface curvature
Elliott et al. use high-resolution imaging, microfabrication and computational analyses to show that the interplay between cell-surface curvature and activity and cortical recruitment of myosin II, control cell migration in 3D matrices.
- Hunter Elliott
- , Robert S. Fischer
- & Gaudenz Danuser
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Article |
The Rho GTPase Rnd1 suppresses mammary tumorigenesis and EMT by restraining Ras-MAPK signalling
Giancotti and colleagues report that the Rnd1 Rho GTPase suppresses the epithelial–mesenchymal transition and mammary tumorigenesis by inhibiting Ras-MAPK signalling through a Plexin B1–Rap1–p120 Ras-GAP signalling axis.
- Tomoyo Okada
- , Surajit Sinha
- & Filippo G. Giancotti
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Letter |
An extracellular-matrix-specific GEF–GAP interaction regulates Rho GTPase crosstalk for 3D collagen migration
Yamada and colleagues report that the interaction of the β-Pix guanine exchange nucleotide factor with the GTPase activating protein, srGAP1, regulates cell migration through collagen by activating Cdc42 and suppressing RhoA activity.
- Matthew L. Kutys
- & Kenneth M. Yamada
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Article |
A Trio–Rac1–Pak1 signalling axis drives invadopodia disassembly
Hodgson and colleagues use a Rac1 biosensor to delineate a signalling pathway that promotes invadopodia dissolution through the activities of the Rac1 GEF Trio, Rac1 and the Pak1 kinase.
- Yasmin Moshfegh
- , Jose Javier Bravo-Cordero
- & Louis Hodgson
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News & Views |
Rho-directed forces in collective migration
Collective cell migration depends on multicellular mechanocoupling between leader and follower cells to coordinate traction force and position change. Co-registration of Rho GTPase activity and forces in migrating epithelial cell sheets now shows how RhoA controls leader–follower cell hierarchy, multicellular cytoskeletal contractility and mechanocoupling, to prevent ectopic leading edges and to move the cell sheet forward.
- Peter Friedl
- , Katarina Wolf
- & Mirjam M. Zegers
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Article |
Interplay of RhoA and mechanical forces in collective cell migration driven by leader cells
Silberzan and colleagues demonstrate that local RhoA activity and mechanical forces control the formation of 'migration fingers', cell protrusions involved in the leader-cell-driven collective migration of epithelial cell monolayers.
- M. Reffay
- , M. C. Parrini
- & P. Silberzan
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News & Views |
Nuanced junctional RhoA activity
RhoA signalling controls many diverse cellular processes, and thus discovering the mechanisms that determine its specific outcomes is a tantalizing challenge. A previously uncharacterized regulatory module operates selectively at the zonula adherens of epithelial cell junctions, in which positive and negative RhoA regulators are coordinated to fine-tune RhoA activity.
- Swapnil S. Kher
- & Rebecca A. Worthylake
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Article |
Centralspindlin and α-catenin regulate Rho signalling at the epithelial zonula adherens
Yap and colleagues identify an extramitotic role for the centralspindlin complex, a Rho signalling regulator during cytokinesis. They show that centralspindlin interacts with α-catenin, and promotes epithelial junctional integrity by recruiting the ECT2 RhoGEF to the zonula adherens, as well as by inhibiting the junctional localization of the p190 B RhoGAP.
- Aparna Ratheesh
- , Guillermo A. Gomez
- & Alpha S. Yap
EGFR ligands dictate tumour suppression
Alan Hall 1952–2015