Identification of a novel conserved sorting motif required for retromer-mediated endosome-to-TGN retrieval.
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.
Seaman
Matthew N J
MN
University of Cambridge, Cambridge Institute for Medical Research/Clinical Biochemistry, Wellcome Trust/MRC building, Addenbrookes Hospital, Cambridge, CB2 0XY, UK. mnjs100@cam.ac.uk
D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D020816:Amino Acid Motifs / Q000235:genetics; D000595:Amino Acid Sequence; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism; D006367:HeLa Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D021381:Protein Transport; D017527:Receptor, IGF Type 2 / Q000737:chemistry* / Q000378:metabolism*; D016415:Sequence Alignment; D018808:Transcription Factor AP-1 / Q000302:isolation & purification / Q000378:metabolism; D014162:Transfection; D022161:Transport Vesicles / Q000378:metabolism; D021601:trans-Golgi Network / Q000737:chemistry / Q000378:metabolism*; D000099183:Sortilin
D033942:Adaptor Proteins, Vesicular Transport; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D017527:Receptor, IGF Type 2; D018808:Transcription Factor AP-1; D000099183:Sortilin