Isolation of Rho GTPase effector pathways during axon development

Michael D. Kim, Daichi Kamiyama, Peter Kolodziej, Huey Hing, Akira Chiba

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

The Rho GTPases Rac1 and Cdc42 have been implicated in the regulation of axon outgrowth and guidance. However, the downstream effector pathways through which these GTPases exert their effects on axon development are not well characterized. Here, we report that axon outgrowth defects within specific subsets of motoneurons expressing constitutively active Drosophila Rac1 largely persist even with the addition of an effector-loop mutation to Rac1 that disrupts its ability to bind to p21-activated kinase (Pak) and other Cdc42/Rac1 interactive-binding (CRIB)-motif effector proteins. While hyperactivation of Pak itself does not lead to axon outgrowth defects as when Rac1 is constitutively activated, live analysis reveals that it can alter filopodial activity within specific subsets of neurons similar to constitutive activation of Cdc42. Moreover, we show that the axon guidance defects induced by constitutive activation of Cdc42 persist even in the absence of Pak activity. Our results suggest that (1) Rac1 controls axon outgrowth through downstream effector pathways distinct from Pak, (2) Cdc42 controls axon guidance through both Pak and other CRIB effectors, and (3) Pak's primary contribution to in vivo axon development is to regulate filopodial dynamics that influence growth cone guidance.

Original languageEnglish (US)
Pages (from-to)282-293
Number of pages12
JournalDevelopmental Biology
Volume262
Issue number2
DOIs
StatePublished - Oct 15 2003

Keywords

  • Axon guidance
  • Cdc42
  • Drosophila
  • Filopodia
  • Growth cone
  • Pak
  • Rac1

ASJC Scopus subject areas

  • Developmental Biology

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