Alpha2-chimaerin Interacts with EphA4 and Regulates EphA4-dependent Growth Cone Collapse

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2007 Oct 4

PMID 17911252

Citations 59

Authors

Lei Shi

Wing-Yu Fu

Kwok-Wang Hung

Cassandra Porchetta

Christine Hall

Amy K Y Fu

Nancy Y Ip

Affiliations

Soon will be listed here.

Abstract

EphA4-dependent growth cone collapse requires reorganization of actin cytoskeleton through coordinated activation of Rho family GTPases. Whereas various guanine exchange factors have recently been identified to be involved in EphA4-mediated regulation of Rho GTPases and growth cone collapse, the functional roles of GTPase-activating proteins in the process are largely unknown. Here we report that EphA4 interacts with alpha2-chimaerin through its Src homology 2 domain. Activated EphA4 induces a rapid increase of tyrosine phosphorylation of alpha2-chimaerin and enhances its GTPase-activating protein activity toward Rac1. More importantly, alpha2-chimaerin regulates the action of EphA4 in growth cone collapse through modulation of Rac1 activity. Our findings have therefore identified a new alpha2-chimaerin-dependent signaling mechanism through which EphA4 transduces its signals to the actin cytoskeleton and modulates growth cone morphology.

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