A third member of the synapsin gene family
A third member of the synapsin gene family
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DOI：
10.1073/pnas.95.8.4667
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发表时间：
1998-04-14
影响因子：
11.1
通讯作者：
Greengard, P
中科院分区：
文献类型：
--
作者：
Kao, HT;Porton, B;Greengard, P
突触是神经元特异性突触囊泡相关的磷蛋白的家族，与突触发生和神经递质释放的调节有关。在哺乳动物中，已经鉴定出突触I和II的不同基因，每种基因都会产生两个剪接的同工型。现在，我们已经克隆并表征了来自人DNA的突触基因家族的第三个成员。突触素III在几种哺乳动物物种中至少产生一种指定的突触素IIIA的蛋白质同工型。突触素IIIA与突触囊泡有关，其表达似乎是神经元特异性的。突触素IIIA的主要结构符合先前针对突触素家族描述的域模型，域A，C和E具有最高的保护程度。突触素IIIA包含一个新的域，称为域J，位于域C和E之间。突触蛋白I，II和III之间的相似性在域组织中，神经元特异性表达和亚细胞定位表明，突触素III可能在调节中起可能作用。神经递质释放和突触发生。人突触III基因位于22q12-13染色体上，该基因已被鉴定为可能的精神分裂症易感基因座。在这种定位和突触的良好神经生物学作用的基础上，突触素III代表了精神分裂症的候选基因。
Synapsins are a family of neuron specific synaptic vesicle-associated phosphoproteins that have been implicated in synaptogenesis and in the modulation of neurotransmitter release. In mammals, distinct genes for synapsins I and II have been identified, each of which gives rise to two alternatively spliced isoforms. We have now cloned and characterized a third member of the synapsin gene family, synapsin III, from human DNA. Synapsin III gives rise to at least one protein isoform, designated synapsin IIIa, in several mammalian species. Synapsin IIIa is associated with synaptic vesicles, and its expression appears to be neuron-specific. The primary structure of synapsin IIIa conforms to the domain model previously described for the synapsin family, with domains A, C, and E exhibiting the highest degree of conservation. Synapsin IIIa contains a novel domain, termed domain J, located between domains C and E. The similarities among synapsins I, II, and III in domain organization, neuron-specific expression, and subcellular localization suggest a possible role for synapsin III in the regulation of neurotransmitter release and synaptogenesis. The human synapsin III gene is located on chromosome 22q12-13, which has been identified as a possible schizophrenia susceptibility locus. On the basis of this localization and the well established neurobiological roles of the synapsins, synapsin III represents a candidate gene for schizophrenia.