Cypin: A cytosolic regulator of PSD-95 postsynaptic targeting
Cypin: A cytosolic regulator of PSD-95 postsynaptic targeting
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DOI：
10.1016/s0896-6273(00)81120-4
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发表时间：
1999-11-01
期刊：
影响因子：
16.2
通讯作者：
Bredt, DS
中科院分区：
文献类型：
--
作者：
Firestein, BL;Brenman, JE;Bredt, DS
突触后密度95（PSD-95/SAP-90）是膜相关鸟苷酸激酶（GK）PDZ蛋白，其在兴奋性突触处支撑谷氨酸受体和相关信号网络。亲和层析鉴定cypin作为脑提取物中的主要PSD-95结合蛋白。Cypin与水解细菌酶家族同源，并与脑信号蛋白III信号传导的细胞质介质-红细胞蛋白反应介质蛋白（CRMP）有一些相似性。Cypin在神经元中离散表达，并且在肠上皮细胞中极化至基底膜。cypin在海马神经元中的过表达特异性地扰乱PSD-95和SAP-102的突触后运输，这是其他PDZ配体的过表达所不产生的效果。事实上，PSD-95可以诱导突触后聚集的，否则弥漫性本地化的K+通道，Kv1.4。cypin通过调节突触后蛋白质的分类，可能影响突触的发育和可塑性。
Postsynaptic density 95 (PSD-95/SAP-90) is a membrane associated guanylate kinase (GK) PDZ protein that scaffolds glutamate receptors and associated signaling networks at excitatory synapses. Affinity chromatography identifies cypin as a major PSD-95-binding protein in brain extracts. Cypin is homologous to a family of hydrolytic bacterial enzymes and shares some similarity with collapsin response mediator protein (CRMP), a cytoplasmic mediator of semaphorin III signalling. Cypin is discretely expressed in neurons and is polarized to basal membranes in intestinal epithelial cells. Overexpression of cypin in hippocampal neurons specifically perturbs postsynaptic trafficking of PSD-95 and SAP-102, an effect not produced by overexpression of other PDZ ligands. In fact, PSD-95 can induce postsynaptic clustering of an otherwise diffusely localized K+ channel, Kv1.4. By regulating postsynaptic protein sorting, cypin may influence synaptic development and plasticity.