Molecular identification of a novel candidate sorting receptor purified from human brain by receptor-associated protein affinity chromatography.

TY - JOUR

T1 - Molecular identification of a novel candidate sorting receptor purified from human brain by receptor-associated protein affinity chromatography.

AU - Petersen, C M

AU - Nielsen, M S

AU - Nykjaer, A

AU - Rasmussen, H H

AU - Roigaard, H

AU - Gliemann, J

AU - Madsen, P

AU - Moestrup, S K

AU - Tommerup, Niels

N1 - Keywords: 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

PY - 1997

Y1 - 1997

N2 - 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.

AB - 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.

M3 - Journal article

C2 - 9013611

SN - 0021-9258

VL - 272

SP - 3599

EP - 3605

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 6

ER -