title: Signaling mechanisms underlying Slit2-induced collapse of Xenopus retinal growth cones.
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.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Piper
authors.forename: Richard
authors.initials: R
authors.lastname: Anderson
authors.forename: Asha
authors.initials: A
authors.lastname: Dwivedy
authors.forename: Christine
authors.initials: C
authors.lastname: Weinl
authors.forename: Francis
authors.initials: F
authors.lastname: van Horck
authors.forename: Kin Mei
authors.initials: KM
authors.lastname: Leung
authors.forename: Emily
authors.initials: E
authors.lastname: Cogill
authors.forename: Christine
authors.initials: C
authors.lastname: Holt
mesh_terms: D051339:Actin Depolymerizing Factors / Q000502:physiology; D000199:Actins / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000502:physiology; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D020439:Growth Cones / Q000502:physiology* / Q000648:ultrastructure; D006497:Heparan Sulfate / Q000502:physiology; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D007930:Leucine / Q000378:metabolism; D008856:Microscopy, Fluorescence; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D009924:Organ Culture Techniques; D011494:Protein Kinases / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012160:Retina / Q000502:physiology* / Q000648:ultrastructure; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases; D014982:Xenopus laevis; D000098552:Slit Homolog 2 Protein
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D006497:Heparan Sulfate; D036341:Intercellular Signaling Peptides and Proteins; D007930:Leucine; D020928:Mitogen-Activated Protein Kinases; D009419:Nerve Tissue Proteins; D011494:Protein Kinases; D012333:RNA, Messenger; D058570:TOR Serine-Threonine Kinases; D000098552:Slit Homolog 2 Protein