Recruitment of active glycogen synthase kinase-3 into neuronal lipid rafts
Recruitment of active glycogen synthase kinase-3 into neuronal lipid rafts
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DOI：
10.1016/j.bbrc.2006.05.087
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发表时间：
2006-07-14
影响因子：
3.1
通讯作者：
Maggirwar, Sanjay B.
中科院分区：
文献类型：
--
作者：
Sui, Ziye;Kovacs, Attila D.;Maggirwar, Sanjay B.
糖原合成酶激酶（GSK）-3 β已经成为调节神经元凋亡的关键分子。为了研究GSK-3 β调节该过程的分子机制，我们研究了细胞暴露于充分表征的凋亡刺激物后GSK-3 β的亚细胞定位。在这里，我们报告，诱导细胞凋亡的血清和钾的撤退触发GSK-3 β丝氨酸9和随后的易位这些分子进入神经元脂筏微结构域的去磷酸化。通过小分子抑制剂抑制GSK-3 P阻断脂筏相关蛋白Tau的特异性磷酸化。与脂筏结构域可作为细胞信号传导复合物的平台的概念一致，脂筏的破坏保护神经元免于由血清和钾的撤回以及由HIV-1达特诱导的细胞凋亡。我们的观察揭示了GSK-3 P和筏结构域的新的相互作用，并表明这种相互作用可能有助于神经元凋亡。(c)2006年爱思唯尔公司All rights reserved.
Glycogen synthase kinase (GSK)-3 beta has emerged as a key molecule that regulates neuronal apoptosis. To examine the molecular mechanism(s) through which GSK-3 beta regulates this process, we studied the subcellular localization of GSK-3 beta following exposure of the cells to well-characterized apoptotic stimuli. Here, we report that the induction of apoptosis by withdrawal of serum and potassium triggers dephosphorylation of GSK-3 beta at serine 9 and Subsequent translocation of these molecules into neuronal lipid raft microdomains. Inhibition of GSK-3P by small molecule inhibitors blocks specific phosphorylation of lipid raft associated protein Tau. Consistent with the notion that the lipid raft domains may serve as a platform for the Cellular Signaling complexes, disruption of lipid rafts protected neurons from apoptosis induced by withdrawal of serum and potassium as well as by HIV-1 Tat. Our observations reveal novel interaction of GSK-3P and raft domains, and suggest that such interaction could contribute to neuronal apoptosis. (c) 2006 Elsevier Inc. All rights reserved.