Degradative organelles containing mislocalized alpha-and beta-synuclein proliferate in presenilin-1 null neurons.
Degradative organelles containing mislocalized alpha-and beta-synuclein proliferate in presenilin-1 null neurons.
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DOI：
10.1083/jcb.200403061
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发表时间：
2004-05-10
期刊：
影响因子：
--
通讯作者：
Lee VM
中科院分区：
文献类型：
--
作者：
Wilson CA;Murphy DD;Giasson BI;Zhang B;Trojanowski JQ;Lee VM
小鼠早老素-1零突变(PS1−/−)与跨膜蛋白的形态改变和切割缺陷有关。在这里，我们证明PS1缺乏也导致退化空泡的形成和突触前α和β突触前突触蛋白的异常移位到初级神经元核膜的这些细胞器，伴随着这两种突触核蛋白水平的显著增加。刺激控制神经元中的自噬产生了与PS1基因消融类似的突触核蛋白的错位。这些效应不是PS1γ分泌酶活性丧失的结果，但可能与PS1−/−细胞钙通道调节失调有关。最后，观察到α-突触核蛋白和降解性细胞器在路易体变异型AD患者的大脑中共存。因此，α-和β-突触核蛋白在退化细胞器中的异常积聚是PS1−/−神经元的新特征，类似的事件可能促进与神经退行性疾病相关的α-突触核蛋白包涵体的形成。
Presenilin-1 null mutation (PS1 −/−) in mice is associated with morphological alterations and defects in cleavage of transmembrane proteins. Here, we demonstrate that PS1 deficiency also leads to the formation of degradative vacuoles and to the aberrant translocation of presynaptic α- and β-synuclein proteins to these organelles in the perikarya of primary neurons, concomitant with significant increases in the levels of both synucleins. Stimulation of autophagy in control neurons produced a similar mislocalization of synucleins as genetic ablation of PS1. These effects were not the result of the loss of PS1 γ-secretase activity; however, dysregulation of calcium channels in PS1 −/− cells may be involved. Finally, colocalization of α-synuclein and degradative organelles was observed in brains from patients with the Lewy body variant of AD. Thus, aberrant accumulation of α- and β-synuclein in degradative organelles are novel features of PS1 −/− neurons, and similar events may promote the formation of α-synuclein inclusions associated with neurodegenerative diseases.
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多特异性语法同源物，VAM3P，对于自噬和生物合成蛋白传输到液泡必不可少。
影响因子：
7.8
作者：
Darsow, T;Rieder, SE;Emr, SD
通讯作者：
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影响因子：
16.2
作者：
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通讯作者：
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影响因子：
64.8
作者：
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通讯作者：
Van Leuven, F
DOI：
10.1073/pnas.052436599
发表时间：
2002-03-05
影响因子：
11.1
作者：
Esler, WP;Kimberly, WT;Wolfe, MS
通讯作者：
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影响因子：
6
作者：
Hsu, LJ;Sagara, Y;Masliah, E
通讯作者：
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