Redistribution of cholesterol in oligodendrocyte membrane sheets after activation of distinct signal transduction pathways
Redistribution of cholesterol in oligodendrocyte membrane sheets after activation of distinct signal transduction pathways
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DOI：
10.1002/(sici)1097-4547(20000515)60:4
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发表时间：
2000-05-15
影响因子：
4.2
通讯作者：
Dyer, CA
中科院分区：
文献类型：
--
作者：
Lintner, RN;Dyer, CA
培养的少突胶质细胞产生广泛的膜片，其内部含有由微管，肌动蛋白丝和2'3'-环核苷酸3'-磷酸水解酶（CNPase）组成的静脉样结构的花边网络，这些细胞质静脉样结构围绕髓鞘碱性蛋白（MBP）的结构域。利用与胆固醇结合的抗生素filipin，研究了细胞膜胆固醇与膜片细胞骨架的关系。我们的结果表明，胆固醇相对均匀地分布在预先控制的少突胶质细胞膜片的质膜内。然而，当用Triton X-100提取活培养物时，胆固醇分子亚群仍然与膜片上的细胞骨架共定位。两种特征明确的信号通路的激活不同程度地影响膜片中的微管和肌动蛋白丝的稳定性，导致胆固醇分子明显地从覆盖在MBP内部结构域上的膜区域向直接覆盖在细胞质细胞骨架静脉上的膜束大量横向移动。秋水仙碱解聚微管导致胆固醇直接在肌动蛋白细丝上重新分布，而细胞松弛素B解聚肌动蛋白细丝导致胆固醇直接在CNPase/微管静脉上重新分布。这些数据表明胆固醇与细胞骨架成分或与细胞骨架相关的蛋白质形成关联，这些数据还表明胆固醇通过与细胞骨架的相互作用，在少突胶质细胞膜片的信号通路中起作用。(C) 2000 Wiley-Liss, Inc；
cultured oligodendrocytes produce extensive membrane sheets that contain an internal lacy network of vein-like structures composed of microtubules, actin filaments, and 2'3'-cyclic nucleotide 3'-phosphohydrolase (CNPase), These cytoplasmic vein-like structures surround domains of myelin basic protein (MBP). Using the antibiotic filipin, that binds to cholesterol, the relationship between plasma membrane cholesterol and cytoskeleton in membrane sheets was examined. Our results show that cholesterol was relatively uniformly distributed within the plasma membranes of prefixed control oligodendrocyte membrane sheets. When live cultures were extracted with Triton X-100, however, a subpopulation of cholesterol molecules remained colocalized with cytoskeleton in the membrane sheets. Activation of two well-characterized signaling pathways that differentially affect microtubule and actin filament stability in membrane sheets resulted in an apparent massive lateral movement of cholesterol molecules away from membrane regions overlying internal MBP domains to membrane tracts directly overlying cytoplasmic cytoskeletal veins. Depolymerization of microtubules by colchicine resulted in redistribution of cholesterol directly over actin filaments, whereas depolymerization of actin filaments by cytochalasin B resulted in redistribution of cholesterol directly over CNPase/microtubular veins. These data suggest that cholesterol forms an association with cytoskeletal components or proteins associated with cytoskeleton, These data also suggest that cholesterol, via interactions with cytoskeleton, plays a role in signaling pathways in oligodendrocyte membrane sheets. (C) 2000 Wiley-Liss, Inc,