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Publication : Angiogenic sprouting requires the fine tuning of endothelial cell cohesion by the Raf-1/Rok-α complex.

First Author  Wimmer R Year  2012
Journal  Dev Cell Volume  22
Issue  1 Pages  158-71
PubMed ID  22209329 Mgi Jnum  J:180124
Mgi Id  MGI:5305501 Doi  10.1016/j.devcel.2011.11.012
Citation  Wimmer R, et al. (2012) Angiogenic Sprouting Requires the Fine Tuning of Endothelial Cell Cohesion by the Raf-1/Rok-alpha Complex. Dev Cell 22(1):158-71
abstractText  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 spatiotemporal 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.
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