Mutations in the SPG3A gene encoding the GTPase atlastin interfere with vesicle trafficking in the ER/Golgi interface and Golgi morphogenesis
Mutations in the SPG3A gene encoding the GTPase atlastin interfere with vesicle trafficking in the ER/Golgi interface and Golgi morphogenesis
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DOI：
10.1016/j.mcn.2007.01.012
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发表时间：
2007-05-01
影响因子：
3.5
通讯作者：
Ruberg, M.
中科院分区：
文献类型：
--
作者：
Namekawa, M.;Muriel, M.-P.;Ruberg, M.
导致常染色体显性纯痉挛性截瘫的SPG3A突变导致了一种新的动力蛋白样大GTPase - atlastin的鉴定。阿联蛋白定位于内质网、高尔基体、神经突和生长锥，并与神经突的生长有关。为了研究它是否在早期分泌系统中发挥其活性，我们在细胞培养中表达了正常和突变的atlastin。GTPase结构域的致病性突变通过阻止内质网囊泡的出芽来干扰高尔基复合物的成熟，而该蛋白其他区域的突变破坏了内质网衍生囊泡的裂变或它们向高尔基靶细胞的迁移。因此，阿特拉斯汀在内质网/高尔基界面的囊泡运输中起作用。此外，atlastin与早期分泌途径中调控囊泡出芽和运输的p24/ emp/gp25L家族蛋白部分共定位，并共同免疫沉淀p24，提示其功能关系有待进一步探讨。(C) 2007爱思唯尔公司版权所有。
Mutations in SPG3A causing autosomal dominant pure spastic paraplegia led to identification of atlastin, a new dynamin-like large GTPase. Atlastin is localized in the endoplasmic reticulum, the Golgi, neurites and growth cones and has been implicated in neurite outgrowth. To investigate whether it exerts its activity in the early secretory system, we expressed normal and mutant atlastin in cell culture. Pathogenic mutations in the GTPase domain interfered with the maturation of Golgi complexes by preventing the budding of vesicles from the endoplasmic reticulum, whereas mutations in other regions of the protein disrupted fission of endoplasmic reticulum-derived vesicles or their migration to their Golgi target. Atlastin, therefore, plays a role in vesicle trafficking in the ER/Golgi interface. Furthermore, atlastin partially co-localized with proteins of the p24/ emp/gp25L family that regulate vesicle budding and trafficking in the early secretory pathway, and co-immunoprecipitated p24, suggesting a functional relationship that should be further explored. (C) 2007 Elsevier Inc. All rights reserved.