Characterization of sorCS1, an alternatively spliced receptor with completely different cytoplasmic domains that mediate different trafficking in cells.
We previously isolated and sequenced murine sorCS1, a type 1 receptor containing a Vps10p-domain and a leucine-rich domain. We now show that human sorCS1 has three isoforms, sorCS1a-c, with completely different cytoplasmic tails and differential expression in tissues. The b tail shows high identity with that of murine sorCS1b, whereas the a and c tails have no reported counterparts. Like the Vps10p-domain receptor family members sortilin and sorLA, sorCS1 is synthesized as a proreceptor that is converted in late Golgi compartments by furin-mediated cleavage. Mature sorCS1 bound its own propeptide with low affinity but none of the ligands previously shown to interact with sortilin and sorLA. In transfected cells, about 10% of sorCS1a was expressed on the cell surface and proved capable of rapid endocytosis in complex with specific antibody, whereas sorCS1b presented a high cell surface expression but essentially no endocytosis, and sorCS1c was intermediate. This is an unusual example of an alternatively spliced single transmembrane receptor with completely different cytoplasmic domains that mediate different trafficking in cells.
Hermey
Guido
G
Department of Medical Biochemistry, University of Aarhus, DK-8000 Aarhus C, Denmark.
Keat
Sady J
SJ
Madsen
Peder
P
Jacobsen
Christian
C
Petersen
Claus M
CM
Gliemann
Jorgen
J
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D006224:Cricetinae; D003593:Cytoplasm / Q000378:metabolism*; D018076:DNA, Complementary / Q000378:metabolism; D004705:Endocytosis; D005091:Exons; D006031:Glycosylation; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007930:Leucine / Q000737:chemistry; D008024:Ligands; D051379:Mice; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D014162:Transfection; D020798:Two-Hybrid System Techniques
D018076:DNA, Complementary; D008024:Ligands; D010455:Peptides; D020033:Protein Isoforms; D011956:Receptors, Cell Surface; C472780:SORCS1 protein, human; D007930:Leucine