Cayman Ataxia-Related Protein is a Presynapse-Specific Caspase-3 Substrate
Cayman Ataxia-Related Protein is a Presynapse-Specific Caspase-3 Substrate
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DOI：
10.1007/s11064-011-0430-5
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发表时间：
2011-07-01
影响因子：
4.4
通讯作者：
Nakagawa, Toshiyuki
中科院分区：
文献类型：
--
作者：
Itoh, Masanori;Li, Shimo;Nakagawa, Toshiyuki
Caspase在细胞凋亡和突触可塑性等生理过程中发挥重要作用。然而，突触处的caspase底物仍不清楚。在这里，我们使用了一个小池人脑cDNA文库的体外切割试验。我们发现突触前蛋白Cayaxin是caspase-3和caspase-7的底物。Cayaxin缺乏会导致开曼共济失调，这是一种以小脑功能障碍和智力低下为特征的疾病。小脑颗粒神经元中Cayaxin的切割依赖于caspase-3的激活。裂解位点位于细胞视网膜和三鸟嘌呤交换因子结构域的上游，产生一个C末端片段，可能在抑制MEK2信号转导中发挥替代作用。因此，我们得出结论，Cayaxin是caspase-3在突触前的一种新底物。
Caspase plays an important role in apoptosis and physiological processes such as synaptic plasticity. However, the caspase substrate at the synapse is still unknown. Here we used an in vitro cleavage assay with a small-pool human brain cDNA library. We identified the presynaptic protein Caytaxin as a substrate of caspase-3 and caspase-7. Deficiency in Caytaxin causes Cayman ataxia, a disorder characterized by cerebellar dysfunction and mental retardation. Caytaxin cleavage in cerebellar granule neurons is dependent on caspase-3 activation. The cleavage site is upstream of the cellular retinal and the TRIO guanine exchange factor domain, producing a C-terminal fragment that may play an alternative role in inhibiting MEK2 signaling. Thus, we concluded that Caytaxin is a novel substrate of caspase-3 at the presynapse.