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Publication : Vav family GEFs link activated Ephs to endocytosis and axon guidance.

First Author  Cowan CW Year  2005
Journal  Neuron Volume  46
Issue  2 Pages  205-17
PubMed ID  15848800 Mgi Jnum  J:98310
Mgi Id  MGI:3577824 Doi  10.1016/j.neuron.2005.03.019
Citation  Cowan CW, et al. (2005) Vav family GEFs link activated Ephs to endocytosis and axon guidance. Neuron 46(2):205-17
abstractText  Ephrin signaling through Eph receptor tyrosine kinases can promote attraction or repulsion of axonal growth cones during development. However, the mechanisms that determine whether Eph signaling promotes attraction or repulsion are not known. We show here that the Rho family GEF Vav2 plays a key role in this process. We find that, during axon guidance, ephrin binding to Ephs triggers Vav-dependent endocytosis of the ligand-receptor complex, thus converting an initially adhesive interaction into a repulsive event. In the absence of Vav proteins, ephrin-Eph endocytosis is blocked, leading to defects in growth cone collapse in vitro and significant defects in the ipsilateral retinogeniculate projections in vivo. These findings suggest an important role for Vav family GEFs as regulators of ligand-receptor endocytosis and determinants of repulsive signaling during axon guidance.
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