Program in Pharmaceutical Sciences and Pharmacogenomics, University of California-San Francisco, San Francisco, CA 94158, USA.
J Cell Biol. 2010 Aug 23;190(4):565-74. doi: 10.1083/jcb.201004060.
Postsynaptic density 95/discs large/zonus occludens-1 (PDZ) domain-interacting motifs, in addition to their well-established roles in protein scaffolding at the cell surface, are proposed to act as cis-acting determinants directing the molecular sorting of transmembrane cargo from endosomes to the plasma membrane. This hypothesis requires the existence of a specific trans-acting PDZ protein that mediates the proposed sorting operation in the endosome membrane. Here, we show that sorting nexin 27 (SNX27) is required for efficient PDZ-directed recycling of the beta(2)-adrenoreceptor (beta(2)AR) from early endosomes. SNX27 mediates this sorting function when expressed at endogenous levels, and its recycling activity requires both PDZ domain-dependent recognition of the beta(2)AR cytoplasmic tail and Phox homology (PX) domain-dependent association with the endosome membrane. These results identify a discrete role of SNX27 in PDZ-directed recycling of a physiologically important signaling receptor, and extend the concept of cargo-specific molecular sorting in the recycling pathway.
突触后密度 95/离散大/紧密连接蛋白-1（PDZ）域相互作用基序，除了在细胞表面的蛋白质支架中具有既定作用外，还被认为是作为顺式作用决定因素，指导跨膜货物从内体到质膜的分子分拣。该假设需要存在一种特定的反式作用 PDZ 蛋白，在内体膜中介导所提出的分拣操作。在这里，我们表明分选连接蛋白 27（SNX27）是从早期内体有效 PDZ 定向回收β2-肾上腺素受体（β2AR）所必需的。当以内源性水平表达时，SNX27 介导这种分拣功能，其回收活性需要 PDZ 结构域依赖性识别β2AR 胞质尾和 Phox 同源（PX）结构域依赖性与内体膜结合。这些结果确定了 SNX27 在 PDZ 定向回收生理上重要的信号受体中的离散作用，并扩展了回收途径中货物特异性分子分拣的概念。
