A novel protein complex linking the δ2 glutamate receptor and autophagy:: Implications for neurodegeneration in Lurcher mice
A novel protein complex linking the δ2 glutamate receptor and autophagy:: Implications for neurodegeneration in Lurcher mice
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DOI：
10.1016/s0896-6273(02)00861-9
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发表时间：
2002-08-29
期刊：
影响因子：
16.2
通讯作者：
Heintz, N
中科院分区：
文献类型：
--
作者：
Yue, ZY;Horton, A;Heintz, N
自噬是亚细胞成分大量降解的途径，在许多神经退行性疾病中过度激活。它被认为是程序性细胞死亡的第二种形式。潜伏动物小脑浦肯野细胞的死亡是由于 GluRdelta2 的突变导致其组成性激活所致。在这里，我们鉴定了 GluRdelta2 和 Beclin1 之间的蛋白质相互作用，GluRdelta2 是一种与该受体结合的包含 PDZ 结构域的蛋白质 (nPIST) 的新亚型。 nPIST 和 Beclin1 可以协同诱导自噬。 GluRdelta2(Lc)，但不是 GluRdelta2(wt)，也可以诱导自噬。此外，垂死的浦肯野细胞含有体内自噬死亡的形态学特征。这些结果提供了强有力的证据，表明 GluRdelta2(Lc) 受体与垂死浦肯野细胞中自噬途径的刺激之间存在直接联系。
Autophagy is a pathway for bulk degradation of subcellular constituents that is hyperactivated in many neurodegenerative conditions. It has been considered a second form of programmed cell death. Death of cerebellar Purkinje cells in lurcher animals is due to a mutation in GluRdelta2 that results in its constitutive activation. Here we have identified protein interactions between GluRdelta2, a novel isoform of a PDZ domain-containing protein (nPIST) that binds to this receptor, and Beclin1. nPIST and Beclin1 can synergize to induce autophagy. GluRdelta2(Lc), but not GluRdelta2(wt), can also induce autophagy. Furthermore, dying lurcher Purkinje cells contain morphological hallmarks of autophagic death in vivo. These results provide strong evidence that a direct link exists between GluRdelta2(Lc) receptor and stimulation of the autophagic pathway in dying lurcher Purkinje cells.