Signaling mechanisms underlying Slit2-induced collapse of Xenopus retinal growth cones.
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.
Piper
Michael
M
Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, United Kingdom.
Anderson
Richard
R
Dwivedy
Asha
A
Weinl
Christine
C
van Horck
Francis
F
Leung
Kin Mei
KM
Cogill
Emily
E
Holt
Christine
C
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
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