Article

Vav Family GEFs Link Activated Ephs to Endocytosis and Axon Guidance

Neurobiology Program, Children's Hospital, Boston, Massachusetts 02115, USA.
Neuron (Impact Factor: 15.98). 05/2005; 46(2):205-17. DOI: 10.1016/j.neuron.2005.03.019
Source: PubMed

ABSTRACT 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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    • "inase - substrate interactions . A unique Eph receptor system involves activation of Eph endocytosis by a membrane - anchored ligand ( ephrin ) ( Pi - tulescu and Adams 2010 ) . In neurons , endocy - tosis of ephrin - EphA4 receptor complex is me - diated by the Rho family guanine exchange factor ( GEF ) Vav2 through an actin - dependent process ( Cowan et al . 2005 ) . Additionally , RIN1 ( Ras binding and Rab5 GEF ) is implicated in EphA4 endocytosis ( Deininger et al . 2008 ) . It is unclear , however , whether EphA4 endocytosis mediated by Vav2 or RIN1 is clathrin depen - dent ."
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