The synaptic vesicle protein CSPα prevents presynaptic degeneration
The synaptic vesicle protein CSPα prevents presynaptic degeneration
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DOI：
10.1016/s0896-6273(04)00190-4
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发表时间：
2004-04-22
期刊：
影响因子：
16.2
通讯作者：
Südhof, TC
中科院分区：
文献类型：
--
作者：
Fernández-Chacón, R;Wölfel, M;Südhof, TC
半胱氨酸串蛋白A（CSPalpha）是一种丰富的突触囊泡蛋白，含有Hsp 40分子伴侣的DNA-J结构域，被认为调节Ca 2+通道和/或突触囊泡胞吐作用。我们现在表明，在年轻的小鼠中，CSPa的缺失不会损害存活率，也不会引起突触前Ca 2+电流或突触囊泡胞吐的显着变化，如在Held突触的萼中所测量的。然而，在2-4周龄时，CSPalpha缺陷小鼠发展为进行性的、致命的感觉运动障碍。CSPA缺陷小鼠的神经肌肉接头和花萼突触表现出神经退行性变化，突触传递严重受损，突变小鼠在近似2个月大时死亡。我们的数据表明，CSPa是不是必不可少的正常操作的Ca 2+通道或胞吐，但作为一个突触前伴侣，保持持续的突触功能，提高了可能性，增强CSPa功能可以减轻神经退行性疾病。
Cysteine string protein a (CSPalpha)-an abundant synaptic vesicle protein that contains a DNA-J domain characteristic of Hsp40 chaperones-is thought to regulate Ca2+ channels and/or synaptic vesicle exocytosis. We now show that, in young mice, deletion of CSPa does not impair survival and causes no significant changes in presynaptic Ca2+ currents or synaptic vesicle exocytosis as measured in the Calyx of Held synapse. At 2-4 weeks of age, however, CSPalpha-deficient mice develop a progressive, fatal sensorimotor disorder. The neuromuscular junctions and Calyx synapses of CSPa-deficient mice exhibit increasing neurodegenerative changes, synaptic transmission becomes severely impaired, and the mutant mice die at similar to2 months of age. Our data suggest that CSPa is not essential for the normal operation of Ca2+ channels or exocytosis but acts as a presynaptic chaperone that maintains continued synaptic function, raising the possibility that enhanced CSPalpha function could attenuate neurodegenerative diseases.