突触融合蛋白 1A 调节多巴胺转运体的活性、磷酸化和表面表达。
Syntaxin 1A regulates dopamine transporter activity, phosphorylation and surface expression.
机构信息
Department of Biochemistry and Molecular Biology, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58203, USA.
出版信息
Neuroscience. 2010 Oct 13;170(2):408-16. doi: 10.1016/j.neuroscience.2010.07.025. Epub 2010 Jul 17.
We investigated the functional relationship between the soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) protein syntaxin 1A (syn 1A) and the dopamine transporter (DAT) by treating rat striatal tissue with Botulinum Neurotoxin C (BoNT/C) and co-transfecting syn 1A with DAT in non-neuronal cells, followed by analysis of DAT activity, phosphorylation, and regulation. Treatment of striatal slices with BoNT/C resulted in elevated dopamine (DA) transport Vmax and reduced DAT phosphorylation, while heterologous co-expression of syn 1A led to reduction in DAT surface expression and transport Vmax. Syn 1A was present in DAT immunoprecipitation complexes, supporting a direct or indirect interaction between the proteins. Phorbol ester regulation of DA transport activity was retained in BoNT/C-treated synaptosomes and syn 1A transfected cells, demonstrating that protein kinase C (PKC) and syn 1A effects occur through independent processes. These findings reveal a novel mechanism for regulation of DAT activity and phosphorylation, and suggest the potential for syn 1A to impact DA neurotransmission through effects on reuptake.
我们通过用肉毒梭菌神经毒素 C（BoNT/C）处理大鼠纹状体组织，并在非神经元细胞中转染突触融合蛋白 1A（syn 1A）与多巴胺转运体（DAT），研究了可溶性 N-乙基马来酰亚胺敏感因子附着蛋白受体（SNARE）蛋白 syntaxin 1A（syn 1A）与 DAT 之间的功能关系，随后分析了 DAT 的活性、磷酸化和调节。BoNT/C 处理纹状体切片可导致多巴胺（DA）转运 Vmax 升高和 DAT 磷酸化减少，而 syn 1A 的异源共表达导致 DAT 表面表达和转运 Vmax 减少。syn 1A 存在于 DAT 免疫沉淀复合物中，支持这两种蛋白质之间的直接或间接相互作用。DAT 转运活性的佛波酯调节在 BoNT/C 处理的突触小体和 syn 1A 转染细胞中得以保留，表明蛋白激酶 C（PKC）和 syn 1A 的作用通过独立的过程发生。这些发现揭示了 DAT 活性和磷酸化调节的新机制，并表明 syn 1A 通过对再摄取的影响，可能会对 DA 神经传递产生影响。
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