Attractive axon guidance involves asymmetric membrane transport and exocytosis in the growth cone
Attractive axon guidance involves asymmetric membrane transport and exocytosis in the growth cone
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DOI：
10.1038/nn1814
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发表时间：
2007-01-01
影响因子：
25
通讯作者：
Kamiguchi, Hiroyuki
中科院分区：
文献类型：
--
作者：
Tojima, Takuro;Akiyama, Hiroki;Kamiguchi, Hiroyuki
生长锥中Ca2+浓度的不对称升高可以介导吸引性和排斥性轴突引导。伴随Ca2+诱导的Ca2+释放（CICR）的Ca2+信号触发吸引，而不伴随CICR的Ca2+信号触发排斥。然而，Ca2+信号下游的分子机制在很大程度上仍然未知。在这里，我们报告说，不对称膜贩运介导的生长锥吸引力。局部光解笼Ca2+，连同CICR，在一侧的小鸡背根神经节神经元的生长锥促进微管依赖性的离心运输的囊泡的前沿和随后的囊泡相关膜蛋白2（VAMP2）介导的胞吐作用的一方与升高的Ca2+浓度。相反，没有CICR的Ca2+信号对囊泡运输没有影响。此外，药理学抑制VAMP2介导的胞吐阻止生长锥吸引，但不排斥。这些结果有力地表明，生长锥的吸引力和排斥力是由不同的机制驱动的，而不是使用具有相反极性的相同分子机制。
Asymmetric elevation of the Ca2+ concentration in the growth cone can mediate both attractive and repulsive axon guidance. Ca2+ signals that are accompanied by Ca2+-induced Ca2+ release (CICR) trigger attraction, whereas Ca2+ signals that are not accompanied by CICR trigger repulsion. The molecular machinery downstream of Ca2+ signals, however, remains largely unknown. Here we report that asymmetric membrane trafficking mediates growth cone attraction. Local photolysis of caged Ca2+, together with CICR, on one side of the growth cone of a chick dorsal root ganglion neuron facilitated the microtubule-dependent centrifugal transport of vesicles towards the leading edge and their subsequent vesicle-associated membrane-protein 2 (VAMP2)-mediated exocytosis on the side with an elevated Ca2+ concentration. In contrast, Ca2+ signals without CICR had no effect on the vesicle transport. Furthermore, pharmacological inhibition of VAMP2-mediated exocytosis prevented growth cone attraction, but not repulsion. These results strongly suggest that growth cone attraction and repulsion are driven by distinct mechanisms, rather than using the same molecular machinery with opposing polarities.