differential regulation of adhesion complex turnover by rock1 and rock2微分调节营业额rock1和rock2粘附复杂.pdfVIP

Differential Regulation of Adhesion Complex Turnover by ROCK1 and ROCK2 1¤ 1 1 2 1 Frances E. Lock , Katie R. Ryan , Natalie S. Poulter , Maddy Parsons , Neil A. Hotchin * 1 School of Biosciences, University of Birmingham, Edgbaston, United Kingdom, 2 Randall Division of Cell and Molecular Biophysics, King’s College London, London, United Kingdom Abstract Background: ROCK1 and ROCK2 are serine/threonine kinases that function downstream of the small GTP-binding protein RhoA. Rho signalling via ROCK regulates a number of cellular functions including organisation of the actin cytoskeleton, cell adhesion and cell migration. Methodology/Principal Findings: In this study we use RNAi to specifically knockdown ROCK1 and ROCK2 and analyse their role in assembly of adhesion complexes in human epidermal keratinocytes. We observe that loss of ROCK1 inhibits signalling via focal adhesion kinase resulting in a failure of immature adhesion complexes to form mature stable focal adhesions. In contrast, loss of ROCK2 expression results in a significant reduction in adhesion complex turnover leading to formation of large, stable focal adhesions. Interestingly, loss of either ROCK1 or ROCK2 expression significantly impairs cell migration indicating both ROCK isoforms are required for normal keratinocyte migration. Conclusions: ROCK1 and ROCK2 have distinct and separate roles in adhesion complex assembly and turnover in human epidermal keratinocytes. Citation: Lock FE, Ryan KR, Poulter NS, Parsons M, Hotchin NA (2012) Differential Regulation of Adhesion Complex Turnover by ROCK1 and ROCK2. PLoS ONE 7(2): e31423. doi:10.1371/journal.pone.0031423 Editor: Robert Alan Arkowitz, Institute of Developmental Biol