Alpha-synuclein and polyunsaturated fatty acids promote clathrin-mediated endocytosis and synaptic vesicle recycling.
Alpha-synuclein and polyunsaturated fatty acids promote clathrin-mediated endocytosis and synaptic vesicle recycling.
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DOI：
10.1111/j.1600-0854.2008.00853.x
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发表时间：
2009-02
期刊：
影响因子：
--
通讯作者：
Sharon R
中科院分区：
文献类型：
--
作者：
Ben Gedalya T;Loeb V;Israeli E;Altschuler Y;Selkoe DJ;Sharon R
α-突触核蛋白（α-Synuclein，αS）是帕金森病（Parkinson's disease，PD）中一种丰富的神经元胞质蛋白，但其生理功能尚不清楚。与其具有与A1类载脂蛋白共享的结构基序一致，αS可以可逆地与膜结合并帮助调节膜脂肪酸（FA）组成。我们先前观察到，多巴胺能培养细胞或脑中αS表达水平的变化与多不饱和脂肪酸（PUFA）水平的变化和膜流动性的改变有关。我们现在报告说，αS与PUFAs一起作用，以增强膜结合染料FM 1-43的内化。具体而言，αS表达与暴露于生理水平的某些PUFA相结合，增强了神经元和非神经元培养细胞中网格蛋白介导的内吞作用。此外，αS表达和PUFA增强野生型和遗传缺失αS小鼠脑的原代海马培养物中基础和诱发的突触囊泡内吞作用。我们认为αS和PUFAs通常在内吞机制中起作用，并且特别参与神经元刺激后突触囊泡的再循环。
α-Synuclein (αS) is an abundant neuronal cytoplasmic protein implicated in Parkinson’s disease (PD), but its physiological function remains unknown. Consistent with its having structural motifs shared with class A1 apolipoproteins, αS can reversibly associate with membranes and help regulate membrane fatty acid (FA) composition. We previously observed that variations in αS expression level in dopaminergic cultured cells or brains are associated with changes in polyunsaturated fatty acid (PUFA) levels and altered membrane fluidity. We now report that αS acts with PUFAs to enhance the internalization of the membrane-binding dye, FM 1-43. Specifically, αS expression coupled with exposure to physiological levels of certain PUFAs enhanced clathrin-mediated endocytosis in neuronal and non-neuronal cultured cells. Moreover, αS expression and PUFA enhanced basal and evoked synaptic vesicle endocytosis in primary hippocampal cultures of wt and genetically depleted αS mouse brains. We suggest that αS, and PUFAs normally functions in endocytic mechanisms and are specifically involved in synaptic vesicle recycling upon neuronal stimulation.
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