Anionic micelles and vesicles induce tau fibrillization in vitro
Anionic micelles and vesicles induce tau fibrillization in vitro
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DOI：
10.1074/jbc.m301663200
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发表时间：
2003-07-11
影响因子：
4.8
通讯作者：
Kuret, J
中科院分区：
文献类型：
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作者：
Chirita, CN;Necula, M;Kuret, J
阿尔茨海默病的部分定义是由由微管相关蛋白tau组成的细丝在神经元内的积累。在体外，重组tau的成纤维化可以通过多种药物诱导，包括磷酸转移酶、多阴离子化合物和脂肪酸。在这里，我们使用重组全长tau蛋白、花生四烯酸和一系列直链阴离子、阳离子和非离子洗涤剂来表征脂肪酸类tau纤化诱导剂所需的结构特征。诱导可测量的tau纤圆化需要至少12个碳的烷基链长度和由羧酸盐、磺酸盐或硫酸盐部分组成的负电荷。所有的洗涤剂和脂肪酸在活性浓度下都是胶束的，这是由于它们的临界胶束浓度的深刻的、tau依赖性的降低。比洗涤剂胶束大的阴离子表面，如由磷脂酰丝氨酸囊泡提供的阴离子表面，也会诱导tau蛋白成纤维，并从其表面产生细丝。这些数据表明，以胶束或囊泡形式出现的阴离子表面可以促进tau蛋白成核，这种机制是脂肪酸诱导剂活性的基础，阴离子膜在体内可能具有这种功能。
Alzheimer's disease is defined in part by the intraneuronal accumulation of filaments comprised of the microtubule-associated protein tau. In vitro, fibrillization of recombinant tau can be induced by treatment with various agents, including phosphotransferases, polyanionic compounds, and fatty acids. Here we characterize the structural features required for the fatty acid class of tau fibrillization inducer using recombinant full-length tau protein, arachidonic acid, and a series of straight chain anionic, cationic, and nonionic detergents. Induction of measurable tau fibrillization required an alkyl chain length of at least 12 carbons and a negative charge consisting of carboxylate, sulfonate, or sulfate moieties. All detergents and fatty acids were micellar at active concentrations, due to a profound, tau-dependent depression of their critical micelle concentrations. Anionic surfaces larger than detergent micelles, such as those supplied by phosphatidylserine vesicles, also induced tau fibrillization with resultant filaments originating from their surface. These data suggest that anionic surfaces presented as micelles or vesicles can serve to nucleate tau fibrillization, that this mechanism underlies the activity of fatty acid inducers, and that anionic membranes may serve this function in vivo.