Assembly-dependent surface targeting of the heterodimeric GABAB receptor is controlled by COPI but not 14-3-3
Assembly-dependent surface targeting of the heterodimeric GABAB receptor is controlled by COPI but not 14-3-3
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DOI：
10.1091/mbc.e05-05-0400
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发表时间：
2005-12-01
影响因子：
3.3
通讯作者：
Pin, JP
中科院分区：
文献类型：
--
作者：
Brock, C;Boudier, L;Pin, JP
细胞表面跨膜蛋白的表达受到严格的调控。与COPI或14-3-3蛋白的相互排斥作用被认为是控制各种蛋白质运输的一种机制。特别是，14-3-3二聚体被提出用来“感应”正确组装的寡聚体，通过阻止COPI介导的细胞内滞留来允许它们的表面靶向。在这里，我们检查了这种机制是否参与了异二聚体G蛋白偶联的GABA(B)受体的质量控制。其携带保留信号RSR的GB1亚基只有在与GB2亚基结合时才能到达细胞表面。我们证明了COPI和14-3-3与GB1 RSR序列特异性结合，并且COPI参与了它在细胞内的滞留。然而，我们证明与14-3-3的相互作用并不是GABA(B)受体质量控制的正常功能所必需的。因此，14-3-3和COPI之间的竞争不能被视为一般的贩运管制机制。讨论了COPI和14-3-3结合之间竞争的另一个可能的作用。
Cell surface expression of transmembrane proteins is strictly regulated. Mutually exclusive interaction with COPI or 14-3-3 proteins has been proposed as a mechanism underlying such trafficking control of various proteins. In particular, 14-3-3 dimers have been proposed to "sense" correctly assembled oligomers, allowing their surface targeting by preventing COPI-mediated intracellular retention. Here we examined whether such a mechanism is involved in the quality control of the heterodimeric G protein-coupled GABA(B) receptor. Its GB1 subunit, carrying the retention signal RSR, only reaches the cell surface when associated with the GB2 subunit. We show that COPI and 14-3-3 specifically bind to the GB1 RSR sequence and that COPI is involved in its intracellular retention. However, we demonstrate that the interaction with 14-3-3 is not required for proper function of the GABA(B) receptor quality control. Accordingly, competition between 14-3-3 and COPI cannot be considered as a general trafficking control mechanism. A possible other role for competition between COPI and 14-3-3 binding is discussed.