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 in | Proceedings of the National Academy of Sciences - PNAS Vol. 104; no. 41; pp. 16347 - 16352 |
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| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
National Academy of Sciences
09.10.2007
National Acad Sciences |
| Subjects | |
| Online Access | Get full text |
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| 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 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. |
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| AbstractList | 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. |
| Author | Hall, Christine Fu, Amy K.Y Fu, Wing-Yu Hung, Kwok-Wang Ip, Nancy Y Porchetta, Cassandra Shi, Lei |
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| Cites_doi | 10.1016/j.neuron.2005.03.019 10.1016/S0092-8674(01)00314-2 10.1523/JNEUROSCI.1170-07.2007 10.1523/JNEUROSCI.22-14-06019.2002 10.1016/j.neuron.2005.06.029 10.1074/jbc.M011368200 10.1128/mcb.13.8.4986-4998.1993 10.1016/S0896-6273(01)00181-7 10.1523/JNEUROSCI.21-14-05191.2001 10.1016/j.neuron.2005.01.030 10.1523/JNEUROSCI.3184-04.2004 10.1002/1097-4695(200008)44:2<126::AID-NEU4>3.0.CO;2-Z 10.1016/j.tcb.2007.03.004 10.1523/JNEUROSCI.0985-04.2004 10.1016/S1044-7431(03)00220-3 10.1242/jcs.02842 10.1038/nn1811 10.1016/S0014-5793(04)00174-7 10.1016/S0959-4388(97)80124-9 |
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| Notes | 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 |
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| SubjectTerms | Antibodies Biological Sciences Brain COS cells Ephrins Growth cones Molecular interactions Neurons Phosphorylation Physiological regulation Receptors |
| Title | α2-Chimaerin interacts with EphA4 and regulates EphA4-dependent growth cone collapse |
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