Co-operative Cdc42 and Rho signalling mediates ephrinB-triggered endothelial cell retraction

Gillian Groeger , Catherine D Nobes (1)

1 Physiology and Biochemistry

Cell repulsion responses to Eph receptor activation are linked to rapid actin cytoskeletal reorganisations, which in turn are partially mediated by Rho-Rho kinase (ROCK) signalling, driving actomyosin contractility. Here we show that Rho alone is not sufficient for this repulsion response. Rather, Cdc42 and its effector MRCK are also critical for ephrinB-induced cell retraction. Stimulation of endothelial cells with ephrin-B2 triggers rapid, but transient, cell retraction. We show that whilst membrane retraction is fully blocked by blebbistatin (a myosin-II ATPase inhibitor), it is only partially blocked by inhibiting Rho-ROCK signalling, suggesting 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.

Mots clés: Life Sciences

Gillian Groeger, Catherine D Nobes. Co-operative Cdc42 and Rho signalling mediates ephrinB-triggered endothelial cell retraction. Biochemical Journal, 2007, 404 (1), pp.23-29. ⟨10.1042/BJ20070146⟩. ⟨hal-00478746⟩