Distinct roles for ROCK1 and ROCK2 in the regulation of cell detachment

dc.contributor.authorShi, Jianjian
dc.contributor.authorWu, Xiangbing
dc.contributor.authorSurma, Michelle
dc.contributor.authorVemula, Sasidhar
dc.contributor.authorZhang, Lumin
dc.contributor.authorYang, Yu
dc.contributor.authorKapur, Reuben
dc.contributor.authorWei, Lei
dc.contributor.departmentPediatrics, School of Medicine
dc.date.accessioned2025-05-27T09:04:08Z
dc.date.available2025-05-27T09:04:08Z
dc.date.issued2013-02-07
dc.description.abstractThis study, using mouse embryonic fibroblast (MEF) cells derived from ROCK1(-/-) and ROCK2(-/-) mice, is designed to dissect roles for ROCK1 and ROCK2 in regulating actin cytoskeleton reorganization induced by doxorubicin, a chemotherapeutic drug. ROCK1(-/-) MEFs exhibited improved actin cytoskeleton stability characterized by attenuated periphery actomyosin ring formation and preserved central stress fibers, associated with decreased myosin light chain 2 (MLC2) phosphorylation but preserved cofilin phosphorylation. These effects resulted in a significant reduction in cell shrinkage, detachment, and predetachment apoptosis. In contrast, ROCK2(-/-) MEFs showed increased periphery membrane folding and impaired cell adhesion, associated with reduced phosphorylation of both MLC2 and cofilin. Treatment with inhibitor of myosin (blebbistatin), inhibitor of actin polymerization (cytochalasin D), and ROCK pan-inhibitor (Y27632) confirmed the contributions of actomyosin contraction and stress fiber instability to stress-induced actin cytoskeleton reorganization. These results support a novel concept that ROCK1 is involved in destabilizing actin cytoskeleton through regulating MLC2 phosphorylation and peripheral actomyosin contraction, whereas ROCK2 is required for stabilizing actin cytoskeleton through regulating cofilin phosphorylation. Consequently, ROCK1 and ROCK2 can be functional different in regulating stress-induced stress fiber disassembly and cell detachment.
dc.eprint.versionFinal published version
dc.identifier.citationShi J, Wu X, Surma M, et al. Distinct roles for ROCK1 and ROCK2 in the regulation of cell detachment. Cell Death Dis. 2013;4(2):e483. Published 2013 Feb 7. doi:10.1038/cddis.2013.10
dc.identifier.urihttps://hdl.handle.net/1805/48360
dc.language.isoen_US
dc.publisherSpringer Nature
dc.relation.isversionof10.1038/cddis.2013.10
dc.relation.journalCell Death & Disease
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.sourcePMC
dc.subjectRho-kinase
dc.subjectActin cytoskeleton remodeling
dc.subjectDetachment
dc.subjectApoptosis
dc.subjectIsoform function
dc.titleDistinct roles for ROCK1 and ROCK2 in the regulation of cell detachment
dc.typeArticle
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