Selective loss of glycogen synthase kinase-3α in birds reveals distinct roles for GSK-3 isozymes in tau phosphorylation
Selective loss of glycogen synthase kinase-3α in birds reveals distinct roles for GSK-3 isozymes in tau phosphorylation
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DOI：
10.1016/j.febslet.2011.03.025
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发表时间：
2011-04-20
期刊：
影响因子：
3.5
通讯作者：
Eldar-Finkelman, Hagit
中科院分区：
文献类型：
--
作者：
Alon, Lina Tsaadon;Pietrokovski, Shmuel;Eldar-Finkelman, Hagit
哺乳动物糖原合成酶激酶 3 (GSK-3) 是神经元信号传导、认知和行为的关键调节因子，以两种同工酶 GSK-3 α 和 GSK-3 β 形式存在。它们独特的生物学功能仍然很大程度上未知。在这里，我们研究了每种同工酶的进化意义。令人惊讶的是，我们发现与其他携带 GSK-3 基因的脊椎动物不同，鸟类中缺少 GSK-3 α 基因。成年鸟类大脑中 GSK-3 介导的 tau 磷酸化显着低于小鼠大脑，这种现象在 GSK-3 α 敲除小鼠大脑中也得到了重现。在鸟类胚胎的大脑中检测到 Tau 磷酸化，表明 GSK-3 同工酶在发育过程中的 tau 磷酸化中发挥着独特的作用。鸟类是天然的 GSK-3 α 基因敲除生物，可作为研究 GSK-3 同工酶独特功能的新模型。 (C) 2011 年欧洲生化学会联合会。由 Elsevier B.V 出版。保留所有权利。
Mammalian glycogen synthase kinase-3 (GSK-3), a critical regulator in neuronal signaling, cognition, and behavior, exists as two isozymes GSK-3 alpha and GSK-3 beta. Their distinct biological functions remains largely unknown. Here, we examined the evolutionary significance of each of these isozymes. Surprisingly, we found that unlike other vertebrates that harbor both GSK-3 genes, the GSK-3 alpha gene is missing in birds. GSK-3-mediated tau phosphorylation was significantly lower in adult bird brains than in mouse brains, a phenomenon that was reproduced in GSK-3 alpha knockout mouse brains. Tau phosphorylation was detected in brains from bird embryos suggesting that GSK-3 isozymes play distinct roles in tau phosphorylation during development. Birds are natural GSK-3 alpha knockout organisms and may serve as a novel model to study the distinct functions of GSK-3 isozymes. (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.