Molecular identification of a novel candidate sorting receptor purified from human brain by receptor-associated protein affinity chromatography.
Receptor-associated protein (RAP) is an endoplasmic reticulum/Golgi protein involved in the processing of receptors of the low density lipoprotein receptor family. A approximately 95-kDa membrane glycoprotein, designated gp95/sortilin, was purified from human brain extracts by RAP affinity chromatography and cloned in a human cDNA library. The gene maps to chromosome ... 1p and encodes an 833-amino acid type I receptor containing an N-terminal furin cleavage site immediately preceding the N terminus determined in the purified protein. Gp95/sortilin is expressed in several tissues including brain, spinal cord, and testis. Gp95/sortilin is not related to the low density lipoprotein receptor family but shows intriguing homologies to established sorting receptors: a 140-amino acid lumenal segment of sortilin representing a hitherto unrecognized type of extracellular module shows extensive homology to corresponding segments in each of the two lumenal domains of yeast Vps10p, and the extreme C terminus of the cytoplasmic tail of sortilin contains the casein kinase phosphorylation consensus site and an adjacent dileucine sorting motif that mediate assembly protein-1 binding and lysosomal sorting of the mannose-6-phosphate receptors. Expression of a chimeric receptor containing the cytoplasmic tail of gp95/sortilin demonstrates evidence that the tail conveys colocalization with the cation-independent mannose6-phosphate receptor in endosomes and the Golgi compartment.
Mesh Terms:
Adaptor Proteins, Vesicular Transport, Amino Acid Sequence, Blotting, Northern, Blotting, Western, Brain Chemistry, Chromatography, Affinity, DNA, Complementary, Humans, Membrane Glycoproteins, Microscopy, Confocal, Molecular Sequence Data, Nerve Tissue Proteins, RNA, Messenger, Recombinant Fusion Proteins, Sequence Alignment, Sequence Homology, Amino Acid
Adaptor Proteins, Vesicular Transport, Amino Acid Sequence, Blotting, Northern, Blotting, Western, Brain Chemistry, Chromatography, Affinity, DNA, Complementary, Humans, Membrane Glycoproteins, Microscopy, Confocal, Molecular Sequence Data, Nerve Tissue Proteins, RNA, Messenger, Recombinant Fusion Proteins, Sequence Alignment, Sequence Homology, Amino Acid
J. Biol. Chem.
Date: Feb. 07, 1997
PubMed ID: 9013611
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