EphB2 receptor forward signaling controls cortical growth cone collapse via Nck and Pak

Nishi Srivastava, Michael A. Robichaux, George Chenaux, Mark Henkemeyer, Christopher W. Cowan

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

EphB receptors and their ephrinB ligands transduce bidirectional signals that mediate contact-dependent axon guidance primarily by promoting growth cone repulsion. However, how EphB receptor-mediated forward signaling induces axonal repulsion remains poorly understood. Here, we identify Nck and Pak proteins as essential forward signaling components of EphB2-dependent growth cone collapse in cortical neurons. We show that kinase-active EphB2 binds to Pak and promotes growth cone repulsion via Pak kinase activity, Pak-Nck binding, RhoA signaling and endocytosis. However, Pak's function in this context appears to be independent of Rac/Cdc42-GTP, consistent with the absence of Rac-GTP production after ephrinB treatment of cortical neurons. Taken together, our findings suggest that ephrinB-activated EphB2 receptors recruit a novel Nck/Pak signaling complex to mediate repulsive cortical growth cone guidance, which may be relevant for EphB forward signaling-dependent axon guidance in vivo.

Original languageEnglish (US)
Pages (from-to)106-116
Number of pages11
JournalMolecular and Cellular Neuroscience
Volume52
DOIs
StatePublished - Jan 2013

Keywords

  • Axon guidance
  • Eph receptor
  • Ephrin
  • Growth cone
  • Signal transduction

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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