Extracellular neurosin degrades α-synuclein in cultured cells
Extracellular neurosin degrades α-synuclein in cultured cells
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DOI：
10.1016/j.neures.2010.04.008
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发表时间：
2010-08-01
影响因子：
2.9
通讯作者：
Tokuda, Takahiko
中科院分区：
文献类型：
--
作者：
Tatebe, Harutsugu;Watanabe, Yoshihisa;Tokuda, Takahiko
神经素，又称激肽释放酶6，是一种主要在中枢神经系统表达的类胰蛋白酶类老年性蛋白水解酶。神经症可能会降解α-突触核蛋白，这是散发性帕金森病患者多巴胺能神经元中常见的路易小体的主要成分。在本研究中，我们利用培养细胞研究了人神经素的定位和蛋白分解活性，以在细胞水平上阐明该酶的生理作用。异源表达的前神经肽原定位于内质网并分泌。用酶谱和荧光底物分析了神经素的蛋白分解活性，结果表明细胞外神经素具有蛋白酶活性，而细胞内神经素不具有蛋白酶活性。我们还共表达了α-突触核蛋白和神经肽，证明了α-突触核蛋白在细胞内不被切割，但细胞外的α-突触核蛋白被分泌的神经素降解。这些发现表明，神经症的目标是细胞外的α-突触核蛋白。(C)2010年爱思唯尔爱尔兰有限公司和日本神经科学学会。版权所有。
Neurosin, also called kallikrein 6, is a trypsin-like senile protease predominantly expressed in the central nervous system. Neurosis may degrade alpha-synuclein, a major component of the Lewy bodies commonly observed in dopaminergic neurons of patients with sporadic Parkinson's disease. In the present study, we investigated the localization and proteolytic activity of human neurosin using cultured cells to elucidate the physiological role of this enzyme at the cellular level. Heterologous expression of pre-pro-neurosin was localized to the endoplasmic reticulum and secreted. The proteolytic activity of neurosin was analyzed by zymography and fluorescent substrate, and showed that extracellular neurosis had protease activity but intracellular neurosin did not. We also coexpressed alpha-synuclein with neurosin and demonstrated that alpha-synuclein was not cleaved within cells, but extracellular alpha-synuclein was degraded by secreted neurosin. These findings suggest that neurosis targets the extracellular alpha-synuclein. (C) 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.