Department of Psychiatry, University of California at San Francisco, San Francisco, California 94158, USA.
Nat Cell Biol. 2011 Jun;13(6):715-21. doi: 10.1038/ncb2252. Epub 2011 May 22.
Endocytic sorting of signalling receptors between recycling and degradative pathways is a key cellular process controlling the surface complement of receptors and, accordingly, the cell's ability to respond to specific extracellular stimuli. The β2 adrenergic receptor (β2AR) is a prototypical seven-transmembrane signalling receptor that recycles rapidly and efficiently to the plasma membrane after ligand-induced endocytosis. β2AR recycling is dependent on the receptor's carboxy-terminal PDZ ligand and Rab4. This active sorting process is required for functional resensitization of β2AR-mediated signalling. Here we show that sequence-directed sorting occurs at the level of entry into retromer tubules and that retromer tubules are associated with Rab4. Furthermore, we show that sorting nexin 27 (SNX27) serves as an essential adaptor protein linking β2ARs to the retromer tubule. SNX27 does not seem to directly interact with the retromer core complex, but does interact with the retromer-associated Wiskott-Aldrich syndrome protein and SCAR homologue (WASH) complex. The present results identify a role for retromer in endocytic trafficking of signalling receptors, in regulating a receptor-linked signalling pathway, and in mediating direct endosome-to-plasma membrane traffic.
内吞信号受体在循环和降解途径之间的分拣是控制受体表面组成的关键细胞过程，因此也是细胞对特定细胞外刺激做出反应的能力的关键。β2 肾上腺素能受体（β2AR）是一种典型的七跨膜信号受体，在配体诱导的内吞作用后，它能快速有效地再循环到质膜。β2AR 的再循环依赖于受体的羧基末端 PDZ 配体和 Rab4。这种主动分拣过程对于β2AR 介导的信号的功能再敏化是必需的。在这里，我们表明序列定向分拣发生在进入逆行小管的水平，并且逆行小管与 Rab4 相关。此外，我们表明分选连接蛋白 27（SNX27）作为将β2AR 与逆行小管连接的必需衔接蛋白。SNX27 似乎不直接与逆行核心复合物相互作用，但与逆行相关的 Wiskott-Aldrich 综合征蛋白和 SCAR 同源物（WASH）复合物相互作用。目前的结果确定了逆行在信号受体的内吞运输、调节受体连接的信号通路以及介导直接内体-质膜运输中的作用。
