Loss of SNAP29 impairs endocytic recycling and cell motility.

Loss of SNAP29 impairs endocytic recycling and cell motility.
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DOI:
10.1371/journal.pone.0009759
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发表时间:
2010-03-18
期刊:
影响因子:
3.7
通讯作者:
Horowitz M
Horowitz M
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Rapaport D;Lugassy Y;Sprecher E;Horowitz M

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细胞内的膜运输依赖于转运中间体的有序形成和消耗,并要求膜以严格调控和高度特异性的方式相互融合。膜锚定的陷阱组装成陷阱复合体,将膜聚集在一起促进融合。SNAP29是一种普遍存在的突触相关SNARE蛋白。它与几种合成素以及含有EH结构域的蛋白EHD1相互作用。功能性SNAP29的缺失导致CEDNIK综合征(脑发育不良、神经病变、鱼鳞病和角化皮肤病)。利用CEDNIK患者的成纤维细胞系,我们发现SNAP29介导了转铁蛋白和β1-整合素的内吞循环。β1整合素循环受损影响了细胞的运动性,这反映在细胞扩散和伤口愈合的变化上。尽管高尔基体系统在SNAP29缺陷细胞中获得了分散的形态,但在高尔基体的VSVG蛋白的胞吐过程中没有发现重大的变化。我们的结果强调了SNAP29介导膜融合在细胞内循环中的重要性,从而在细胞运动中。
Intracellular membrane trafficking depends on the ordered formation and consumption of transport intermediates and requires that membranes fuse with each other in a tightly regulated and highly specific manner. Membrane anchored SNAREs assemble into SNARE complexes that bring membranes together to promote fusion. SNAP29 is a ubiquitous synaptosomal-associated SNARE protein. It interacts with several syntaxins and with the EH domain containing protein EHD1. Loss of functional SNAP29 results in CEDNIK syndrome (Cerebral Dysgenesis, Neuropathy, Ichthyosis and Keratoderma). Using fibroblast cell lines derived from CEDNIK patients, we show that SNAP29 mediates endocytic recycling of transferrin and β1-integrin. Impaired β1-integrin recycling affected cell motility, as reflected by changes in cell spreading and wound healing. No major changes were detected in exocytosis of VSVG protein from the Golgi apparatus, although the Golgi system acquired a dispersed morphology in SNAP29 deficient cells. Our results emphasize the importance of SNAP29 mediated membrane fusion in endocytic recycling and consequently, in cell motility.
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