Cell repulsion responses to Eph receptor activation are linked to rapid actin cytoskeletal reorganizations, which in turn are partially mediated by Rho–ROCK (Rho kinase) signalling, driving actomyosin contractility. In the present study, we show that Rho alone is not sufficient for this repulsion response. Rather, Cdc42 (cell division cycle 42) and its effector MRCK (myotonic dystrophy kinase-related Cdc42-binding kinase) are also critical for ephrinB-induced cell retraction. Stimulation of endothelial cells with ephrinB2 triggers rapid, but transient, cell retraction. We show that, although membrane retraction is fully blocked by blebbistatin (a myosin-II ATPase inhibitor), it is only partially blocked by inhibiting Rho–ROCK signalling, suggesting that there is ROCK-independent signalling to actomyosin contractility downstream of EphBs. We find that a combination of either Cdc42 or MRCK inhibition with ROCK inhibition completely abolishes the repulsion response. Additionally, endocytosis of ephrin–Eph complexes is not required for initial cell retraction, but is essential for subsequent Rac-mediated re-spreading of cells. Our data reveal a complex interplay of Rho, Rac and Cdc42 in the process of EphB-mediated cell retraction–recovery responses.
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Research Article|
April 26 2007
Co-operative Cdc42 and Rho signalling mediates ephrinB-triggered endothelial cell retraction
Gillian Groeger;
Gillian Groeger
*Department of Physiology, School of Medical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, U.K.
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Catherine D. Nobes
Catherine D. Nobes
1
*Department of Physiology, School of Medical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, U.K.
†Department of Biochemistry, School of Medical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, U.K.
1To whom correspondence should be addressed (email catherine.nobes@bristol.ac.uk).
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Publisher: Portland Press Ltd
Received:
January 26 2007
Accepted:
February 14 2007
Accepted Manuscript online:
February 14 2007
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2007 Biochemical Society
2007
Biochem J (2007) 404 (1): 23–29.
Article history
Received:
January 26 2007
Accepted:
February 14 2007
Accepted Manuscript online:
February 14 2007
Citation
Gillian Groeger, Catherine D. Nobes; Co-operative Cdc42 and Rho signalling mediates ephrinB-triggered endothelial cell retraction. Biochem J 15 May 2007; 404 (1): 23–29. doi: https://doi.org/10.1042/BJ20070146
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