ROCK1 and 2 differentially regulate actomyosin organization to drive cell and synaptic polarity
| Autor: | Karen Newell-Litwa, Hannelore Asmussen, Mathilde Badoual, Heather Patel, Leanna Whitmore, Alan Rick Horwitz |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Dendritic spine
RHOA Dendritic Spines macromolecular substances CHO Cells Biology Article Actin remodeling of neurons Mice Cricetulus Cell Movement Cricetinae Cell polarity Cell Adhesion Animals Humans ROCK1 Actin Research Articles rho-Associated Kinases Actin remodeling Cell Polarity Cell Biology Actomyosin Actin cytoskeleton musculoskeletal system Cell biology Rats Protein Transport Actin Depolymerizing Factors Synapses biology.protein |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| Popis: | ROCK1 forms the stable actomyosin filament bundles that initiate front–back and dendritic spine polarity, while ROCK2 regulates contractile force, Rac1 activity, and cofilin-mediated actin remodeling at the leading edge of migratory cells and the spine head of neurons. 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. |
| Databáze: | OpenAIRE |
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