Eph-dependent tyrosine phosphorylation of ephexin1 modulates growth cone collapse

Mustafa Sahin, Paul L. Greer, Michael Z. Lin, Heather Poucher, Johann Eberhart, Susanne Schmidt, Tracy M. Wright, Steven M. Shamah, Sinead O'Connell, Christopher W. Cowan, Linda Hu, Jeffrey L. Goldberg, Anne Debant, Gabriel Corfas, Catherine E. Krull, Michael E. Greenberg

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171 Scopus citations

Abstract

Ephs regulate growth cone repulsion, a process controlled by the actin cytoskeleton. The guanine nucleotide exchange factor (GEF) ephexin1 interacts with EphA4 and has been suggested to mediate the effect of EphA on the activity of Rho GTPases, key regulators of the cytoskeleton and axon guidance. Using cultured ephexin1-/- mouse neurons and RNA interference in the chick, we report that ephexin1 is required for normal axon outgrowth and ephrin-dependent axon repulsion. Ephexin1 becomes tyrosine phosphorylated in response to EphA signaling in neurons, and this phosphorylation event is required for growth cone collapse. Tyrosine phosphorylation of ephexin1 enhances ephexin1's GEF activity toward RhoA while not altering its activity toward Rac1 or Cdc42, thus changing the balance of GTPase activities. These findings reveal that ephexin1 plays a role in axon guidance and is regulated by a switch mechanism that is specifically tailored to control Eph-mediated growth cone collapse.

Original languageEnglish (US)
Pages (from-to)191-204
Number of pages14
JournalNeuron
Volume46
Issue number2
DOIs
StatePublished - Apr 21 2005

ASJC Scopus subject areas

  • Neuroscience(all)

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    Sahin, M., Greer, P. L., Lin, M. Z., Poucher, H., Eberhart, J., Schmidt, S., Wright, T. M., Shamah, S. M., O'Connell, S., Cowan, C. W., Hu, L., Goldberg, J. L., Debant, A., Corfas, G., Krull, C. E., & Greenberg, M. E. (2005). Eph-dependent tyrosine phosphorylation of ephexin1 modulates growth cone collapse. Neuron, 46(2), 191-204. https://doi.org/10.1016/j.neuron.2005.01.030