Transmembrane molecular pump activity of Niemann-Pick C1 protein
Transmembrane molecular pump activity of Niemann-Pick C1 protein
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DOI：
10.1126/science.290.5500.2295
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发表时间：
2000-12-22
期刊：
影响因子：
56.9
通讯作者：
Ioannou, YA
中科院分区：
文献类型：
--
作者：
Davies, JP;Chen, FW;Ioannou, YA
尼曼-匹克C1（NPC 1）病的特征是胆固醇在溶酶体中积聚和细胞胆固醇稳态的异常反馈调节。我们提供的证据表明NPC 1蛋白与原核通透酶的抗性-增殖-分裂（RND）家族具有同源性，并且可能正常地起跨膜外排泵的作用，在正常和NPC 1成纤维细胞中的吖啶黄负载的研究表明，NPC 1使用质子动力从内体/溶酶体系统中去除积累的吖啶黄。NPC 1在大肠杆菌中的表达（i）促进了吖啶黄跨质膜的转运，引起胞质积累，（ii）导致油酸而不是胆固醇或胆固醇-油酸酯跨质膜的转运。这些研究确定NPC 1为RND通透酶家族的真核成员。
Niemann-Pick C1 (NPC1) disease is characterized by cholesterol accumulation in Lysosomes and aberrant feedback regulation of cellular cholesterol homeostasis, We provide evidence that the NPC1 protein has homology with the resistance-nodulation-division (RND) family of prokaryotic permeases and may normally function as a transmembrane efflux pump, Studies of acriflavine Loading in normal and NPC1 fibroblasts indicated that NPC1 uses a proton motive force to remove accumulated acriflavine from the endosomal/lysosomal system. Expression of NPC1 in Escherichia coli (i) facilitated the transport of acriflavine across the plasma membrane, causing cytosolic accumulation, and (ii) resulted in transport of oleic acid but not cholesterol or cholesterol-oleate across the plasma membrane. These studies establish NPC1 as a eukaryotic member of the RND permease family.