Apolipoprotein A-I increases association of cytosolic cholesterol and caveolin-1 with microtubule cytoskeletons in rat astrocytes
Apolipoprotein A-I increases association of cytosolic cholesterol and caveolin-1 with microtubule cytoskeletons in rat astrocytes
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DOI：
10.1111/j.1471-4159.2006.03805.x
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发表时间：
2006-05-01
影响因子：
4.7
通讯作者：
Yokoyama, S
中科院分区：
文献类型：
--
作者：
Ito, J;Kheirollah, A;Yokoyama, S
载脂蛋白（apo）A-I诱导蛋白激酶C α和磷脂酶C γ的快速移位，以及小窝蛋白-1和新合成的胆固醇缓慢移位到大鼠星形胶质细胞的胞质脂质蛋白颗粒（CLPP）组分。为了了解CLPP的功能，我们研究了与CLPP相关的蛋白质，如小窝蛋白-1和蛋白激酶C α和CLPP相关的脂质在大鼠星形胶质细胞的细胞骨架的相互作用。微管解聚的条件下，与蛋白激酶C α和α-微管蛋白的胞质小窝蛋白-1的协会被增强时，细胞用载脂蛋白A-I处理5分钟。这种协会被抑制的小窝蛋白-1的支架结构域肽。与微管样丝的胞质脂质，小窝蛋白-1和蛋白激酶C α的协会也增加了载脂蛋白A-I治疗和抑制的支架结构域肽。紫杉醇（紫杉醇），一种稳定微管的化合物，抑制apoA-I介导的细胞内易位和从头合成的胆固醇和磷脂从细胞中释放。这些发现表明，CLPP与微管的关联是由小窝蛋白-1的支架结构域介导的，由apoA-I诱导，并参与调节细胞内胆固醇运输，以将细胞脂质组装成apoA-I-高密度脂蛋白（HDL）。
Apolipoprotein (apo) A-I induces rapid translocation of protein kinase C alpha and phospholipase C gamma, and slow translocation of caveolin-1 and newly synthesized cholesterol to the cytosolic lipid-protein particle (CLPP) fraction in rat astrocytes. In order to understand the function of CLPP, we investigated the interaction with cytoskeletons of CLPP-related proteins such as caveolin-1 and protein kinase C alpha and of CLPP-related lipids in rat astrocytes. Under the conditions that microtubules were depolymerized, association of cytosolic caveolin-1 with protein kinase C alpha and alpha-tubulin was enhanced when the cells were treated with apoA-I for 5 min. This association was suppressed by a scaffolding domain-peptide of caveolin-1. Association with the microtubule-like filaments of cytosolic lipids, caveolin-1 and protein kinase C alpha was also increased by the apoA-I treatment and inhibited by the scaffolding domain peptide. Paclitaxel (taxol), a compound to stabilize microtubules, suppressed the apoA-I-mediated intracellular translocation and release from the cells of the de novo synthesized cholesterol and phospholipid. The findings suggested that the association of CLPP with microtubules is mediated by a scaffolding domain of caveolin-1, induced by apoA-I and involved in regulation of intracellular cholesterol trafficking for assembly of cellular lipids to apoA-I-high-density lipoprotein (HDL).