Modulation of the SNARE core complex by dopamine
Modulation of the SNARE core complex by dopamine
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DOI：
10.1139/cjpp-78-10-856
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发表时间：
2000-10-01
影响因子：
2.1
通讯作者：
Braun, JEA
中科院分区：
文献类型：
--
作者：
Fisher, H;Braun, JEA
大脑中神经细胞之间的交流主要是通过称为突触的特殊连接进行的。最近，突触传递的许多细节已经浮出水面。对突触囊泡释放起重要作用的特定蛋白的特性现已确定。我们研究了三种突触蛋白，VAMP（囊泡相关膜蛋白，也称为突触brevin）， syntaxin和SNAP25 （25kDa的突触体相关蛋白）作为多巴胺介导的大鼠纹状体切片突触功能调节的可能靶点。这三种蛋白形成一个SNARE（可溶性n -乙基马来酰胺敏感因子附着蛋白受体）核心复合物，已知其对突触传递至关重要。虽然可以设想SNAREs经过动态和循环的相互作用来引发突触囊泡释放，但它们在神经传递中的确切功能仍不清楚。我们在完整的大鼠纹状体切片中检测了SNARE复合物。细胞蛋白溶解，SDS-PAGE电泳分离，免疫鉴定。将多巴胺应用于纹状体切片导致SNAREs倾向于SNARE核心复合物，这是一种在没有交联剂的情况下自发形成的复合物，而不是单体形式。此外，多巴胺处理的纹状体切片的快速交联表明，多巴胺处理的纹状体切片中SNARE复合物比对照片增加了4倍。氟哌啶醇阻断了多巴胺引起的核心复合物的变化。这些结果表明，SNAREs活动的变化可能涉及多巴胺调节纹状体突触可塑性的潜在细胞机制。
Communication between nerve cells in the brain occurs primarily through specialized junctions called synapses. Recently, many details of synaptic transmission have emerged. The identities of specific proteins important for synaptic vesicle release have now been established. We have investigated three synaptic proteins, VAMP (vesicle associated membrane protein; also called synaptobrevin), syntaxin, and SNAP25 (synaptosomal associated protein of 25kDa) as possible targets in the dopamine-mediated modulation of synaptic function in rat striatal slices. These three proteins form a SNARE (soluble N-ethylmalemide-sensitive factor attachment protein receptors) core complex that is known to be essential for synaptic transmission. Although it is envisioned that the SNAREs undergo dynamic and cyclic interactions to elicit synaptic vesicle release, their precise functions in neurotransmission remains unknown. We have examined SNARE complexes in intact rat striatal slices. Cellular proteins were solubilized, separated electrophoretically by SDS-PAGE, and then identified immunologically. Application of dopamine to striatal slices results in SNAREs favoring the SNARE core complex, a complex which forms spontaneously in the absence of crosslinking agents, rather than the monomer form. In addition, rapid crosslinking of dopamine-treated striatal slices demonstrates that the SNARE complex is increased 4 fold in dopamine treated striatal slices compared with control slices. Haloperidol blocked the dopamine-induced change in the core complex. These results suggest that changes in the activities of SNAREs may be involved in the underlying cellular mechanisms(s) of dopamine-regulated synaptic plasticity of the striatum.