Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Traffic. 2012 Oct;13(10):1315-25. doi: 10.1111/j.1600-0854.2012.01396.x. Epub 2012 Jul 24.
The GGA family of clathrin adaptor proteins mediates the intracellular trafficking of transmembrane proteins by interacting with DXXLL-type sorting signals on the latter. These signals were originally identified at the carboxy-termini of the transmembrane cargo proteins. Subsequent studies, however, showed that internal DXXLL sorting motifs occur within the N- or C-terminal cytoplasmic domains of cargo molecules. The GGAs themselves also contain internal DXXLL motifs that serve to auto-regulate GGA function. A recent study challenged the notion that internal DXXLL signals are competent for binding to GGAs. Since the question of whether GGA adaptors interact with internal DXXLL motifs is fundamental to the identification of bona fide GGA cargo, and to an accurate understanding of GGA regulation within cells, we have extended our previous findings. We now present additional evidence confirming that GGAs do interact with internal DXXLL motifs. We also summarize the recent reports from other laboratories documenting internal GGA binding motifs.
网格蛋白衔接蛋白家族通过与跨膜蛋白上的 DXXLL 型分拣信号相互作用，介导跨膜蛋白的细胞内运输。这些信号最初是在跨膜货物蛋白的羧基末端被识别的。然而，随后的研究表明，内部 DXXLL 分拣基序存在于货物分子的 N-或 C-末端细胞质域内。GGAs 本身也含有内部 DXXLL 基序，用于自身调节 GGA 功能。最近的一项研究质疑了内部 DXXLL 信号是否能够与 GGAs 结合的观点。由于 GGA 衔接蛋白是否与内部 DXXLL 基序相互作用，是鉴定真正的 GGA 货物以及准确理解细胞内 GGA 调节的基础，因此我们扩展了之前的发现。我们现在提供了更多的证据证实 GGAs 确实与内部 DXXLL 基序相互作用。我们还总结了其他实验室最近的报告，记录了内部 GGA 结合基序。
