Signaling Mechanisms Underlying Slit2-Induced Collapse of Xenopus Retinal Growth Cones Academic Article uri icon

abstract

  • Slits mediate multiple axon guidance decisions, but the mechanisms underlying the responses of growth cones to these cues remain poorly defined. We show here that collapse induced by Slit2-conditioned medium (Slit2-CM) in Xenopus retinal growth cones requires local protein synthesis (PS) and endocytosis. Slit2-CM elicits rapid activation of translation regulators and MAP kinases in growth cones, and inhibition of MAPKs or disruption of heparan sulfate blocks Slit2-CM-induced PS and repulsion. Interestingly, Slit2-CM causes a fast PS-dependent decrease in cytoskeletal F-actin concomitant with a PS-dependent increase in the actin-depolymerizing protein cofilin. Our findings reveal an unexpected link between Slit2 and cofilin in growth cones and suggest that local translation of actin regulatory proteins contributes to repulsion.

authors

  • Piper, Michael
  • Anderson, Richard
  • Dwivedy, Asha
  • Weinl, Christine
  • van Horck, Francis
  • Leung, Kin Mei
  • Cogill, Emily
  • Holt, Christine

publication date

  • January 2006

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