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RhoA and ROCK promote migration by limiting membrane protrusions
Rebecca A Worthylake1, Keith Burridge
1Department of Cell and Developmental Biology, Lineberger Comprehensive Cancer Center and Comprehensive Center for Inflammatory Disorders, University of North Carolina, Chapel Hill, North Carolina 27599, USA. becky_worthlake@med.unc.edu
The Journal of Biological Chemistry
|February 8, 2003
Summary
RhoA/ROCK signaling restricts integrin adhesion and membrane protrusions, promoting leukocyte migration. Inhibiting ROCK increases adhesion and protrusions, while inhibiting RhoA disrupts monocyte migration by causing competing lamellipodia.
Area of Science:
- Cellular Biology
- Molecular Biology
- Immunology
Background:
- RhoA and Rho-associated protein kinase (ROCK) signaling are known regulators of leukocyte migration.
- These pathways are involved in controlling integrin-mediated adhesion and cell retraction during migration.
Purpose of the Study:
- To elucidate the molecular mechanisms by which RhoA/ROCK signaling regulates integrin adhesion.
- To investigate the role of ROCK in controlling actin cytoskeleton remodeling and membrane dynamics during cell migration.
Main Methods:
- Inhibition of ROCK and RhoA signaling pathways.
- Analysis of integrin-mediated adhesion, phosphotyrosine signaling (Pyk-2, paxillin), and actin cytoskeleton.
- Assessment of membrane protrusion formation and cell migration dynamics in leukocytes and monocytes.
Main Results:
- ROCK inhibition up-regulates integrin adhesion, increases Pyk-2/paxillin signaling, and causes aberrant membrane protrusions.
- ROCK inhibition promotes integrin adhesion via actin cytoskeleton remodeling and regulates membrane activity through cofilin.
- RhoA inhibition leads to multiple lamellipodia, disrupting productive monocyte migration.
Conclusions:
- RhoA/ROCK signaling is crucial for restricting integrin activity and membrane protrusions to the leading edge of migrating cells.
- This precise regulation by RhoA/ROCK signaling is essential for promoting efficient and directed leukocyte migration.