RINT-1 regulates the localization and entry of ZW10 to the Syntaxin 18 complex
RINT-1 regulates the localization and entry of ZW10 to the Syntaxin 18 complex
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DOI：
10.1091/mbc.e05-10-0973
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发表时间：
2006-06-01
影响因子：
3.3
通讯作者：
Tagaya, Mitsuo
中科院分区：
文献类型：
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作者：
Arasaki, Kohei;Taniguchi, May;Tagaya, Mitsuo
RINT-1最初被鉴定为参与辐射诱导的G（2）/M检查点控制的Rad 50相互作用蛋白。我们最近报道，RINT-1，连同dynamitin相互作用蛋白ZW 10和其他人，是与syntaxin 18，内质网（ER）的本地化陷阱参与膜之间的ER和高尔基体的运输。为了解决RINT-1在膜运输中的作用，我们研究了RINT-1的过表达和敲低对高尔基体形态和ER蛋白转运的影响。负责与ZW 10相互作用的RINT-1的N-末端区域的过表达引起ZW 10的再分布。同时，内质网到高尔基体的转运被阻断，高尔基体被分散。RINT-1的敲除也破坏了ER和高尔基体之间的膜运输。值得注意的是，RINT-1的沉默导致与突触融合蛋白18相关的ZW 10的量减少，伴随着ZW 10的再分布。相反，当ZW 10表达降低时，没有观察到RINT-1从突触融合蛋白18复合物中的重新分布或释放。这些结果共同表明，RINT-1通过充当ZW 10和包含突触融合蛋白18的SNARE复合物之间的联系来协调ZW 10的定位和功能。
RINT-1 was first identified as a Rad50-interacting protein that participates in radiation-induced G(2)/M checkpoint control. We have recently reported that RINT-1, together with the dynamitin-interacting protein ZW10 and others, is associated with syntaxin 18, an endoplasmic reticulum (ER)-localized SNARE involved in membrane trafficking between the ER and Golgi. To address the role of RINT-1 in membrane trafficking, we examined the effects of overexpression and knockdown of RINT-1 on Golgi morphology and protein transport from the ER. Overexpression of the N-terminal region of RINT-1, which is responsible for the interaction with ZW10, caused redistribution of ZW10. Concomitantly, ER-to-Golgi transport was blocked and the Golgi was dispersed. Knockdown of RINT-1 also disrupted membrane trafficking between the ER and Golgi. Notably, silencing of RINT-1 resulted in a reduction in the amount of ZW10 associated with syntaxin 18, concomitant with ZW10 redistribution. In contrast, no redistribution or release of RINT-1 from the syntaxin 18 complex was observed when ZW10 expression was reduced. These results taken together suggest that RINT-1 coordinates the localization and function of ZW10 by serving as a link between ZW10 and the SNARE complex comprising syntaxin 18.