Signaling mechanisms underlying Slit2-induced collapse of Xenopus retinal growth cones

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

doi:10.1016/j.neuron.2005.12.008

Signaling mechanisms underlying Slit2-induced collapse of Xenopus retinal growth cones

Neuron. 2006 Jan 19;49(2):215-28. doi: 10.1016/j.neuron.2005.12.008.

Authors

Michael Piper¹, Richard Anderson, Asha Dwivedy, Christine Weinl, Francis van Horck, Kin Mei Leung, Emily Cogill, Christine Holt

Affiliation

¹ Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, United Kingdom.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Actin Depolymerizing Factors / physiology
Actins / metabolism
Animals
Axons / physiology
Endocytosis / drug effects
Endocytosis / physiology
Gene Expression Regulation / physiology
Growth Cones / physiology*
Growth Cones / ultrastructure
Heparitin Sulfate / physiology
Immunoprecipitation
In Situ Hybridization
Intercellular Signaling Peptides and Proteins
Leucine / metabolism
Microscopy, Fluorescence
Mitogen-Activated Protein Kinases / physiology
Nerve Tissue Proteins / biosynthesis
Nerve Tissue Proteins / drug effects
Nerve Tissue Proteins / genetics*
Nerve Tissue Proteins / physiology*
Organ Culture Techniques
Protein Kinases / physiology
RNA, Messenger / biosynthesis
RNA, Messenger / genetics
Retina / physiology*
Retina / ultrastructure
Signal Transduction / physiology*
TOR Serine-Threonine Kinases
Xenopus laevis

Substances

Actin Depolymerizing Factors
Actins
Intercellular Signaling Peptides and Proteins
Nerve Tissue Proteins
RNA, Messenger
Heparitin Sulfate
Protein Kinases
TOR Serine-Threonine Kinases
Mitogen-Activated Protein Kinases
Leucine
Slit homolog 2 protein

Grants and funding

070568/Wellcome Trust/United Kingdom