RAB ESCORT PROTEIN-1 IS A MULTIFUNCTIONAL PROTEIN THAT ACCOMPANIES NEWLY PRENYLATED RAB PROTEINS TO THEIR TARGET MEMBRANES
RAB ESCORT PROTEIN-1 IS A MULTIFUNCTIONAL PROTEIN THAT ACCOMPANIES NEWLY PRENYLATED RAB PROTEINS TO THEIR TARGET MEMBRANES
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DOI：
10.1002/j.1460-2075.1994.tb06860.x
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发表时间：
1994-11-15
期刊：
影响因子：
11.4
通讯作者：
ZERIAL, M
中科院分区：
文献类型：
--
作者：
ALEXANDROV, K;HORIUCHI, H;ZERIAL, M
Rab蛋白包括在囊泡膜运输中起调节作用的小GTP酶家族。这些蛋白质在C-末端半胱氨酸基序上的香叶基香叶基化对其膜缔合和功能至关重要。这种翻译后修饰由rab香叶基香叶基转移酶（RabGGT酶）催化，RabGGT酶是一种多亚基酶，由催化异源二聚体和辅助组分组成，称为rab护送蛋白（REP）-1。先前的体外研究表明REP-1将新合成的rab蛋白呈递给酶的催化组分，并在转移反应后与异戊烯化蛋白形成稳定的复合物。根据该模型，将需要细胞因子来使rab蛋白与REP-1解离并使其在异戊烯化反应中再循环。RabGDP解离抑制剂（RabGDI）被认为是该作用的理想候选物，因为其在介导异戊烯化的rab蛋白的膜缔合中的既定功能。在这里，我们表明，从REP-1和rab蛋白的膜结合解离不需要RabGDI或其他胞质因子。REP-1介导的rab 5膜结合的机制似乎与RabGDI介导的机制非常相似。此外，REP-1和RabGDI共享几个其他的功能特性，抑制GDP的释放和从膜中去除rab蛋白的能力;然而，RabGDI不能帮助异戊烯化反应。这些数据表明，REP-1本身足以陪伴新的异戊二烯化的rab蛋白到它们的靶膜。
Rab proteins comprise a family of small GTPases that serve a regulatory role in vesicular membrane traffic. Geranylgeranylation of these proteins on C-terminal cysteine motifs is crucial for their membrane association and function. This post-translational modification is catalysed by rab geranylgeranyl transferase (RabGGTase), a multisubunit enzyme consisting of a catalytic heterodimer and an accessory component, named rab escort protein (REP)-1. Previous in vitro studies have suggested that REP-1 presents newly synthesized rab proteins to the catalytic component of the enzyme, and forms a stable complex with the prenylated proteins following the transfer reaction. According to this model, a cellular factor would be required to dissociate the rab protein from REP-1 and to allow it to recycle in the prenylation reaction. RabGDP dissociation inhibitor (RabGDI) was considered an ideal candidate for this role, given its established function in mediating membrane association of prenylated rab proteins. Here we demonstrate that dissociation from REP-1 and binding of rab proteins to the membrane do not require RabGDI or other cytosolic factors. The mechanism of REP-1-mediated membrane association of rab5 appears to be very similar to that mediated by RabGDI. Furthermore, REP-1 and RabGDI share several other functional properties, the ability to inhibit the release of GDP and to remove rab proteins from membranes; however, RabGDI cannot assist in the prenylation reaction. These data suggest that REP-1 is per se sufficient to chaperone newly prenylated rab proteins to their target membranes.