Asymmetric membrane ganglioside sialidase activity specifies axonal fate
Asymmetric membrane ganglioside sialidase activity specifies axonal fate
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DOI：
10.1038/nn1442
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发表时间：
2005-05-01
影响因子：
25
通讯作者：
Abad-Rodriguez, J
中科院分区：
文献类型：
--
作者：
Da Silva, JS;Hasegawa, T;Abad-Rodriguez, J
轴突特化触发神经元的极化，需要丝状肌动蛋白的局部不稳定。在这里，我们表明，质膜神经节苷脂唾液酸酶（PMGS）不对称积累在一个未极化的大鼠神经元的轴突尖端，诱导肌动蛋白不稳定。抑制PMGS活性会阻断轴突的生成，而刺激它会加速单个（而不是几个）轴突的形成。PMGS通过局部增强TrkA活性诱导轴突特化，这触发磷脂酰肌醇-3-激酶（PI 3 K）-和Rac 1-依赖性抑制RhoA信号传导和随后仅在一个神经突中的肌动蛋白解聚。因此，在极化之前，肌动蛋白调节分子机制的空间限制（在这种情况下是膜酶活性）足以决定轴突的命运。
Axon specification triggers the polarization of neurons and requires the localized destabilization of filamentous actin. Here we show that plasma membrane ganglioside sialidase (PMGS) asymmetrically accumulates at the tip of one neurite of the unpolarized rat neuron, inducing actin instability. Suppressing PMGS activity blocks axonal generation, whereas stimulating it accelerates the formation of a single (not several) axon. PMGS induces axon specification by enhancing TrkA activity locally, which triggers phosphatidylinositol-3-kinase (PI3K)- and Rac1-dependent inhibition of RhoA signaling and the consequent actin depolymerization in one neurite only. Thus, spatial restriction of an actin-regulating molecular machinery, in this case a membrane enzymatic activity, before polarization is enough to determine axonal fate.