Sterol binding by OSBP-related protein 1L regulates late endosome motility and function
Sterol binding by OSBP-related protein 1L regulates late endosome motility and function
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DOI：
10.1007/s00018-010-0470-z
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发表时间：
2011-02-01
影响因子：
8
通讯作者：
Olkkonen, Vesa M.
中科院分区：
文献类型：
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作者：
Vihervaara, Terhi;Uronen, Riikka-Liisa;Olkkonen, Vesa M.
ORP1L是一种调节晚期核内体（LE）定位的氧甾醇结合同源物。我们发现ORP1L结合几种氧甾醇和胆固醇，并描述了一个突变体ORP1L Delta 560-563，在氧甾醇结合方面存在缺陷。与野生型ORP1L簇LE不同，ORP1L Delta 560-563诱导LE散射，并通过破坏靶向FFAT基序的内质网（ER）而逆转，这表明这是由于LE-ER相互作用增强所致。ORP1L过表达会降低核内体的运动。野生型ORP1L和Delta 560-563突变体均诱导LE上dynactin和kinesin-2的募集。大部分被过表达的ORP1L修饰的LE不能接受内吞葡聚糖或EGF，转染的细胞对内化的EGF表现出缺陷降解。巨噬细胞泡沫细胞ORP1L沉默增强内核体运动，抑制[H-3]胆固醇向载脂蛋白A-I的外排。这些数据表明，在蛋白质和脂质运输中，LE的运动和功能都受到ORP1L的调节。
ORP1L is an oxysterol binding homologue that regulates late endosome (LE) positioning. We show that ORP1L binds several oxysterols and cholesterol, and characterize a mutant, ORP1L Delta 560-563, defective in oxysterol binding. While wild-type ORP1L clusters LE, ORP1L Delta 560-563 induces LE scattering, which is reversed by disruption of the endoplasmic reticulum (ER) targeting FFAT motif, suggesting that it is due to enhanced LE-ER interactions. Endosome motility is reduced upon overexpression of ORP1L. Both wild-type ORP1L and the Delta 560-563 mutant induce the recruitment of both dynactin and kinesin-2 on LE. Most of the LE decorated by overexpressed ORP1L fail to accept endocytosed dextran or EGF, and the transfected cells display defective degradation of internalized EGF. ORP1L silencing in macrophage foam cells enhances endosome motility and results in inhibition of [H-3]cholesterol efflux to apolipoprotein A-I. These data demonstrate that LE motility and functions in both protein and lipid transport are regulated by ORP1L.