Goshima Y, Nakamura F, Strittmatter P, Strittmatter S M
Department of Neurology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Nature. 1995 Aug 10;376(6540):509-14. doi: 10.1038/376509a0.
Collapsin, a member of the newly recognized semaphorin family, contributes to axonal pathfinding during neural development by inhibiting growth cone extension. The mechanism of collapsin action is poorly understood. Here we use a Xenopus laevis oocyte expression system to identify molecules involved in collapsin signalling, because several experiments have raised the possibility that heterotrimeric GTP-binding proteins might participate in these events. A collapsin response mediator protein of relative molecular mass (M(r)) 62K (CRMP-62) required for collapsin-induced inward currents in X. laevis oocytes is isolated. CRMP-62 shares homology with UNC-33, a nematode neuronal protein required for appropriately directed axonal extension. CRMP-62 is localized exclusively in the developing chick nervous system. Introduction of anti-CRMP-62 antibodies into dorsal root ganglion neurons blocks collapsin-induced growth cone collapse. CRMP-62 appears to be an intracellular component of a signalling cascade initiated by an unidentified transmembrane collapsin-binding protein.
塌陷蛋白是新发现的信号素家族的成员之一，通过抑制生长锥延伸，在神经发育过程中对轴突导向起作用。塌陷蛋白的作用机制尚不清楚。由于多项实验提出异源三聚体GTP结合蛋白可能参与这些事件，我们在此使用非洲爪蟾卵母细胞表达系统来鉴定参与塌陷蛋白信号传导的分子。我们分离出了非洲爪蟾卵母细胞中塌陷蛋白诱导内向电流所需的相对分子质量（M(r)）为62K的塌陷蛋白反应介导蛋白（CRMP - 62）。CRMP - 62与UNC - 33具有同源性，UNC - 33是一种线虫神经元蛋白，对轴突的正确定向延伸是必需的。CRMP - 62仅定位于发育中的鸡神经系统。将抗CRMP - 62抗体引入背根神经节神经元会阻断塌陷蛋白诱导的生长锥塌陷。CRMP - 62似乎是由一种未知的跨膜塌陷蛋白结合蛋白启动的信号级联反应的细胞内成分。
