α2-Chimaerin interacts with EphA4 and regulates EphA4-dependent growth cone collapse

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 fun...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 104; no. 41; pp. 16347 - 16352
Main Authors Shi, Lei, Fu, Wing-Yu, Hung, Kwok-Wang, Porchetta, Cassandra, Hall, Christine, Fu, Amy K.Y, Ip, Nancy Y
Format Journal Article
LanguageEnglish
Published National Academy of Sciences 09.10.2007
National Acad Sciences
Subjects
Antibodies
Biological Sciences
Brain
COS cells
Ephrins
Growth cones
Molecular interactions
Neurons
Phosphorylation
Physiological regulation
Receptors
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Summary: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 α2-chimaerin through its Src homology 2 domain. Activated EphA4 induces a rapid increase of tyrosine phosphorylation of α2-chimaerin and enhances its GTPase-activating protein activity toward Rac1. More importantly, α2-chimaerin regulates the action of EphA4 in growth cone collapse through modulation of Rac1 activity. Our findings have therefore identified a new α2-chimaerin-dependent signaling mechanism through which EphA4 transduces its signals to the actin cytoskeleton and modulates growth cone morphology.
Bibliography:Author contributions: L.S., W.-Y.F., A.K.Y.F., and N.Y.I. designed research; L.S., W.-Y.F., and K.-W.H. performed research; C.P. and C.H. contributed new reagents/analytic tools; L.S., W.-Y.F., K.-W.H., C.H., A.K.Y.F., and N.Y.I. analyzed data; and L.S., A.K.Y.F., and N.Y.I. wrote the paper.
Edited by Eric M. Shooter, Stanford University School of Medicine, Stanford, CA, and approved August 31, 2007
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0706626104