Alpha2-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 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.
Shi
Lei
L
Department of Biochemistry, Biotechnology Research Institute, and Molecular Neuroscience Center, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
Fu
Wing-Yu
WY
Hung
Kwok-Wang
KW
Porchetta
Cassandra
C
Hall
Christine
C
Fu
Amy K Y
AK
Ip
Nancy Y
NY
D000199:Actins / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000254:growth & development* / Q000378:metabolism*; D002460:Cell Line; D020848:Chimerin 1 / Q000737:chemistry / Q000378:metabolism*; D020439:Growth Cones / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D009474:Neurons / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D036122:Receptor, EphA4 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction; D014443:Tyrosine / Q000737:chemistry; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
D000199:Actins; D020848:Chimerin 1; D011994:Recombinant Proteins; D014443:Tyrosine; D036122:Receptor, EphA4; D020830:rac1 GTP-Binding Protein