Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adaptor Proteins, Vesicular Transport / metabolism
-
Amino Acid Motifs* / genetics
-
Amino Acid Sequence
-
Endocytosis
-
Endosomes / metabolism*
-
Golgi Apparatus / metabolism
-
HeLa Cells / cytology
-
HeLa Cells / metabolism*
-
Humans
-
Membrane Glycoproteins / chemistry
-
Membrane Glycoproteins / isolation & purification
-
Membrane Glycoproteins / metabolism*
-
Molecular Sequence Data
-
Nerve Tissue Proteins / chemistry
-
Nerve Tissue Proteins / isolation & purification
-
Nerve Tissue Proteins / metabolism*
-
Protein Transport
-
Receptor, IGF Type 2 / chemistry*
-
Receptor, IGF Type 2 / metabolism*
-
Sequence Alignment
-
Transcription Factor AP-1 / isolation & purification
-
Transcription Factor AP-1 / metabolism
-
Transfection
-
Transport Vesicles / metabolism
-
trans-Golgi Network / chemistry
-
trans-Golgi Network / metabolism*
Substances
-
Adaptor Proteins, Vesicular Transport
-
Membrane Glycoproteins
-
Nerve Tissue Proteins
-
Receptor, IGF Type 2
-
Transcription Factor AP-1
-
sortilin