Rabaptin-5α/rabaptin-4 serves as a linker between rab4 and γ1-adaptin in membrane recycling from endosomes
Rabaptin-5α/rabaptin-4 serves as a linker between rab4 and γ1-adaptin in membrane recycling from endosomes
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DOI：
10.1093/emboj/cdg257
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发表时间：
2003-06-02
期刊：
影响因子：
11.4
通讯作者：
van der Sluijs, P
中科院分区：
文献类型：
--
作者：
Deneka, M;Neeft, M;van der Sluijs, P
Rab 4调节早期内体的再循环。我们研究了rab 4效应子rabaptin-5 α及其假定的伴侣gamma（1）-adaptin在膜再循环中的作用。我们发现，rabaptin-5 α通过与γ（1）-亚基的直接相互作用，与AP-1的γ（1）-σ（1）亚复合物形成三元复合物。γ（1）-适配蛋白的结合位点位于rabaptin-5 α的铰链区，其不同于rab 4-和rab 5-结合结构域。内源性或异位表达的gamma（1）- adaptin定位于trans-Golgi网络和内涵体。然而，共表达的rabaptin-5 α和gamma（1）-adaptin以rab 4依赖性方式共定位于再循环内体上。rabaptin-5 α的转染引起扩大的内体和延迟的转铁蛋白再循环。rab 4的RNAi对转铁蛋白再循环具有相反的作用。总的来说，我们的数据表明，rab 4-GTP作为再生核内体上的rabaptin-5 α-γ（1）-适应素复合物的支架，并且rab 4、rabaptin-5 α和γ（1）-适应素之间的相互作用调节膜再生。
Rab4 regulates recycling from early endosomes. We investigated the role of the rab4 effector rabaptin-5alpha and its putative partner gamma(1)-adaptin in membrane recycling. We found that rabaptin-5alpha forms a ternary complex with the gamma(1)-sigma(1) subcomplex of AP-1, via a direct interaction with the gamma(1)-subunit. The binding site for gamma(1)-adaptin is in the hinge region of rabaptin-5alpha, which is distinct from rab4- and rab5-binding domains. Endogenous or ectopically expressed gamma(1)- adaptin localized to both the trans-Golgi network and endosomes. Co-expressed rabaptin-5alpha and gamma(1)-adaptin, however, co-localized in a rab4-dependent manner on recycling endosomes. Transfection of rabaptin-5alpha caused enlarged endosomes and delayed recycling of transferrin. RNAi of rab4 had an opposing effect on transferrin recycling. Collectively, our data show that rab4-GTP acts as a scaffold for a rabaptin-5alpha- gamma(1)-adaptin complex on recycling endosomes and that interactions between rab4, rabaptin-5alpha and gamma(1)-adaptin regulate membrane recycling.