Angiogenic Sprouting Requires the Fine Tuning of Endothelial Cell Cohesion by the Raf-1/Rok-alpha Complex

作者：Wimmer Reiner; Cseh Botond; Maier Barbara; Scherrer Karina; Baccarini Manuela^*

来源：Developmental Cell, 2012, 22(1): 158-171.

DOI：10.1016/j.devcel.2011.11.012

Sprouting angiogenesis, crucial for the development of new blood vessels, is a prime example of collective migration in which endothelial cells migrate as a group joined via cadherin-containing adherens junctions (AJ). The actomyosin apparatus is connected to AJ and generates contractile forces, which, depending on their strength and duration, increase or decrease cell cohesion. Thus, appropriate spatio-temporal control of junctional myosin is critical, but the mechanisms underlying it are incompletely understood. We show that Raf-1 is an essential component of this regulatory network and that its ablation impairs endothelial cell cohesion, sprouting, and tumor-induced angiogenesis. Mechanistically, Raf-1 is recruited to VE-cadherin complexes by a mechanism involving the small G protein Rap1 and is required to bring the Rho effector Rok-alpha to nascent AJs. This Raf-1-mediated fine tuning of Rok-alpha signaling allows the activation of junctional myosin and the timely maturation of AJ essential for maintaining cell cohesion during sprouting angiogenesis.

• 出版日期2012-1-17