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