ROCK1 and 2 differentially regulate actomyosin organization to drive cell and synaptic polarity |
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| Authors: | Karen A. Newell-Litwa Mathilde Badoual Hannelore Asmussen Heather Patel Leanna Whitmore Alan Rick Horwitz |
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| Affiliation: | 1.Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, VA 22908;2.Laboratoire Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC), UMR 8165, Centre National de la Recherche Scientifique, University Paris-Sud and University Paris Diderot, 91405 Orsay, France |
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| Abstract: | RhoGTPases organize the actin cytoskeleton to generate diverse polarities, from front–back polarity in migrating cells to dendritic spine morphology in neurons. For example, RhoA through its effector kinase, RhoA kinase (ROCK), activates myosin II to form actomyosin filament bundles and large adhesions that locally inhibit and thereby polarize Rac1-driven actin polymerization to the protrusions of migratory fibroblasts and the head of dendritic spines. We have found that the two ROCK isoforms, ROCK1 and ROCK2, differentially regulate distinct molecular pathways downstream of RhoA, and their coordinated activities drive polarity in both cell migration and synapse formation. In particular, ROCK1 forms the stable actomyosin filament bundles that initiate front–back and dendritic spine polarity. In contrast, ROCK2 regulates contractile force and Rac1 activity at the leading edge of migratory cells and the spine head of neurons; it also specifically regulates cofilin-mediated actin remodeling that underlies the maturation of adhesions and the postsynaptic density of dendritic spines. |
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