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果蝇突触小泡蛋白基因的鉴定与特征分析。

Identification and characterization of Drosophila genes for synaptic vesicle proteins.

作者信息

DiAntonio A, Burgess R W, Chin A C, Deitcher D L, Scheller R H, Schwarz T L

机构信息

Department of Molecular and Cellular Physiology, Stanford University Medical Center, California 94305-5426.

出版信息

J Neurosci. 1993 Nov;13(11):4924-35. doi: 10.1523/JNEUROSCI.13-11-04924.1993.

Abstract

Proteins associated with synaptic vesicles are likely to control the release of neurotransmitter. Because synaptic transmission is fundamentally similar between vertebrates and invertebrates, vesicle proteins from vertebrates that are important for synaptic transmission should be present in Drosophila as well. This investigation describes Drosophila homologs of vamp, synaptotagmin, and rab3 that are expressed in a pattern consistent with a function in Drosophila neurotransmission. One previously reported candidate (syb), a Drosophila homolog of the vamp or synaptobrevin proteins, has been shown to be expressed at very low levels in neurons and is most abundant in the gut. A neuronal Drosophila vamp (n-syb) is described here and is localized to chromosome band 62A. Northern analysis and in situ hybridizations to mRNA indicate that the novel vamp, as well as the genes for synaptotagmin (syt) and rab3 (drab3), is expressed in the Drosophila nervous system. These genes are widely (perhaps ubiquitously) expressed in the nervous system and we have no evidence of additional neuronal isoforms of synaptotagmin, vamp, or rab3. Immunoreactivity for synaptotagmin and vamp is located in synaptic regions of the nervous system. This distribution suggests that these molecules are components of synaptic vesicles in Drosophila. The conserved structure and neuronal expression pattern of these genes indicate that they may function in processes that are required for both vertebrate and invertebrate synaptic transmission. Because of their distribution in the nervous system and because n-syb, synaptotagmin, and drab3 do not appear to be in a family of functionally redundant homologs, we predict that mutation of these genes will have a profound neurological phenotype and that they are therefore good candidates for a genetic dissection in Drosophila.

摘要

与突触小泡相关的蛋白质可能控制神经递质的释放。由于脊椎动物和无脊椎动物之间的突触传递在根本上是相似的,对脊椎动物突触传递重要的小泡蛋白在果蝇中也应该存在。本研究描述了vamp、突触结合蛋白和rab3在果蝇中的同源物,它们的表达模式与在果蝇神经传递中的功能一致。一个先前报道的候选物(syb),即vamp或突触融合蛋白的果蝇同源物,已被证明在神经元中表达水平极低,在肠道中最为丰富。这里描述了一种神经元果蝇vamp(n-syb),它定位于染色体带62A。对mRNA的Northern分析和原位杂交表明,新的vamp以及突触结合蛋白(syt)和rab3(drab3)的基因在果蝇神经系统中表达。这些基因在神经系统中广泛(可能普遍)表达,我们没有证据表明突触结合蛋白、vamp或rab3存在其他神经元亚型。突触结合蛋白和vamp的免疫反应性位于神经系统的突触区域。这种分布表明这些分子是果蝇突触小泡的组成部分。这些基因保守的结构和神经元表达模式表明它们可能在脊椎动物和无脊椎动物突触传递所需的过程中发挥作用。由于它们在神经系统中的分布,并且由于n-syb、突触结合蛋白和drab3似乎不属于功能冗余同源物家族,我们预测这些基因的突变将产生深刻的神经表型,因此它们是果蝇遗传剖析的良好候选对象。

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