ZFPL1, a novel ring finger protein required for cis-Golgi integrity and efficient ER-to-Golgi transport

ZFPL1, a novel ring finger protein required for cis-Golgi integrity and efficient ER-to-Golgi transport
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DOI:
10.1038/emboj.2008.40
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发表时间:
2008-04-09
期刊:
影响因子:
11.4
通讯作者:
Lowe, Martin
Lowe, Martin
中科院分区:
生物学1区
文献类型:
--
作者:
Chiu, Chi-Fang;Ghanekar, Yashoda;Lowe, Martin

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高尔基体在分泌途径中占据中心位置,但对其组装和组织的分子机制仍知之甚少。我们在这里报告的锌指蛋白样1(ZFPL1)作为一种新的结构组成部分的高尔基体的鉴定。ZFPL1是一种保守的、广泛表达的膜蛋白,其N端有两个锌指,第二个锌指可能是一个环状结构域。ZFPL 1直接与顺式高尔基体基质蛋白GM 130相互作用。ZFPL 1的缺失导致中间室(IC)中顺式高尔基体基质蛋白的积累以及顺式高尔基体和IC膜的微管。ZFPL 1功能的丧失也损害了布雷菲德菌素A洗脱后的顺式高尔基体组装,并减缓了货物运输到高尔基体的速率。野生型ZFPL1可以挽救高尔基体基质蛋白定位和顺式高尔基体结构的影响,但不能挽救GM130结合缺陷的突变体。总之,这些数据表明,ZFPL1在维持顺式高尔基体的完整性方面具有重要功能,并且它通过与GM130的相互作用来实现。
The Golgi apparatus occupies a central position within the secretory pathway, but the molecular mechanisms responsible for its assembly and organization remain poorly understood. We report here the identification of zinc finger protein-like 1 (ZFPL1) as a novel structural component of the Golgi apparatus. ZFPL1 is a conserved and widely expressed integral membrane protein with two predicted zinc fingers at the N-terminus, the second of which is a likely ring domain. ZFPL1 directly interacts with the cis-Golgi matrix protein GM130. Depletion of ZFPL1 results in the accumulation of cis-Golgi matrix proteins in the intermediate compartment (IC) and the tubulation of cis-Golgi and IC membranes. Loss of ZFPL1 function also impairs cis-Golgi assembly following brefeldin A washout and slows the rate of cargo trafficking into the Golgi apparatus. Effects upon Golgi matrix protein localization and cis-Golgi structure can be rescued by wild-type ZFPL1 but not mutants defective in GM130 binding. Together, these data suggest that ZFPL1 has an important function in maintaining the integrity of the cis-Golgi and that it does so through interactions with GM130.