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

被引:225
作者
Piper, M [1 ]
Anderson, R [1 ]
Dwivedy, A [1 ]
Weinl, C [1 ]
van Horck, F [1 ]
Leung, KM [1 ]
Cogill, E [1 ]
Holt, C [1 ]
机构
[1] Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge, England
基金
英国惠康基金;
关键词
D O I
10.1016/j.neuron.2005.12.008
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:215 / 228
页数:14
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