Seaman Matthew N J
University of Cambridge, Cambridge Institute for Medical Research/Clinical Biochemistry, Wellcome Trust/MRC building, Addenbrookes Hospital, Cambridge, CB2 0XY, UK.
J Cell Sci. 2007 Jul 15;120(Pt 14):2378-89. doi: 10.1242/jcs.009654.
The cation-independent mannose 6-phosphate receptor (CIMPR) cycles between the trans-Golgi network (TGN) and endosomes to mediate sorting of lysosomal hydrolases. The endosome-to-TGN retrieval of the CIMPR requires the retromer complex. Genetic, biochemical and structural data support the hypothesis that the retromer can directly bind to the tail of the CIMPR, to sort the CIMPR into vesicles and tubules for retrieval to the TGN. Presently, however, no known retromer sorting motif in the tail of the CIMPR has been identified. Using CD8-reporter proteins carrying the cytoplasmic tail of the CIMPR we have systematically dissected the CIMPR tail to identify a novel, conserved aromatic-containing sorting motif that is critical for the endosome-to-TGN retrieval of the CIMPR and for the interaction with retromer and the clathrin adaptor AP-1.
不依赖阳离子的甘露糖6-磷酸受体（CIMPR）在反式高尔基体网络（TGN）和内体之间循环，以介导溶酶体水解酶的分选。CIMPR从内体到TGN的回收需要逆向转运复合物。遗传学、生物化学和结构数据支持这样的假说，即逆向转运复合物可直接结合CIMPR的尾部，将CIMPR分选到囊泡和小管中，以便回收到TGN。然而，目前尚未在CIMPR的尾部鉴定出已知的逆向转运复合物分选基序。我们使用携带CIMPR细胞质尾部的CD8报告蛋白，系统地剖析了CIMPR尾部，以鉴定一种新的、保守的含芳香族氨基酸的分选基序，该基序对于CIMPR从内体到TGN的回收以及与逆向转运复合物和网格蛋白衔接蛋白AP-1的相互作用至关重要。
