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Regulation of membrane traffic between the ER and Golgi by SNARE-associated proteins, ZW10/RINT-1

SNARE 相关蛋白 ZW10/RINT-1 调节 ER 和高尔基体之间的膜交通

基本信息

批准号：
18370081
负责人：
TAGAYA Mitsuo
金额：
$ 10.9万
依托单位：
Tokyo University of Pharmacy and Life Science
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18370081/
关键词：
Svntaxin 18 ZW10 RINT-1 Dvnein Dvnactin Endoplasmic reticulum Microtubules Vesicular transport Sintaxin18 Syntaxin18

项目摘要

SNAREs (Soluble NSF attachment protein receptors) are involved in membrane fusion in the vesicular transport pathways in eukaryotic cells. We previously reported that syntaxin 18, a mammalian ER-localized SNARE, forms a complex with other SNAREs (BNIP1, p31, and Sec22b) and peripheral membrane proteins ZW10, and RINT-1). In the present study, we examined the function of a ZW10/RINT-1 complex in membrane traffic between the ER and the Golgi apparatus, and obtained the following results.1) Interaction between ZW10 and dynamitinProtein transport from the ER to the Golgi is mediated by the microtubule motor protein dynein-dynactin. We found that dynamitin, a subunit of the dynactin complex, and RINT-1 bind to the N-terminal region of ZW10 in a competitive manner. Evidence for the in vivo interaction of the N-terminal region of ZW10 with dynamitin was obtained by using nordihydroguaiaretic acid, a reagent that is known to stimulate dynein-dynactin-mediated processes. These results raise the possibility that ZW10 on the ER membrane is recruited to transport carriers through the interaction with dynamitin.2) Interaction of ZW10 with coatomer subunitsCOPI-coated vesicles are responsible for protein transport from the ER to the Golgi in mammalian cells. Binding experiments revealed that β,γ, and δ-COPI, weakly interact with ZW10, supporting the idea that ZW10 exists on COPI-coated vesicles and acts as a dynein-dynactin receptor.3) The NAG (Neuroblastoma amplified gene) product interacts with ZW10/RINT-1We discovered that NAG is a component of the syntaxin 18 complex. The N-terminal region of NAG interacts with the N-terminal region of p31, and the C-terminal region of NAG bind ZW10/RINT-1.

SNARES(可溶性NSF附着蛋白受体)参与了真核细胞囊泡转运途径的膜融合。我们先前报道，Synaxin 18是一种哺乳动物内质网定位的SNARE，它与其他SNARs(BNIP1、p31和Sec22b)以及外周膜蛋白ZW10和Rint-1形成复合体。在本研究中，我们研究了ZW10/Rint-1复合体在内质网和高尔基体之间的膜运输中的作用，得到了以下结果：1)ZW10和Dynamitin1之间的相互作用是由微管运动蛋白dynein-dynactin介导的。我们发现动力蛋白复合体的亚基Dynamitin和Rint-1以竞争的方式与ZW10的N端区域结合。使用去甲二氢愈创木酸获得了ZW10的N-末端区域与动力蛋白在体内相互作用的证据，去甲二氢愈创木酸是一种已知的刺激动力蛋白-动力蛋白介导的过程的试剂。这些结果增加了ZW10通过与动力的相互作用被招募来运输载体的可能性。2)ZW10与辅瘤亚单位的相互作用在哺乳动物细胞中负责蛋白质从内质网到高尔基体的运输。结合实验表明，β，γ和δ-CoPI与ZW10存在弱相互作用，支持ZW10存在于包被CoPI的囊泡上并作为动力蛋白-动力蛋白受体的观点。3)NAG(神经母细胞瘤扩增基因)产物与ZW10/RINT-1相互作用发现NAG是Synaxin 18复合体的一个组成部分。NAG的N末端区域与P31的N末端区域相互作用，NAG的C末端区域与ZW10/Rint-1结合。