Molecular polymorphism of the syndecans. Identification of a hypo-glycanated murine syndecan-1 splice variant.
We have identified a cDNA that encodes a variant form of murine syndecan-1. The variant cDNA lacks the sequence corresponding to the first 132 nucleotides of the third exon of the syndecan-1 gene. The corresponding message is rare. The alternative splice respects the reading frame and deletes 44 amino acids from the protein, joining the S45GS47GT sequence to a variant immediate downstream context. This sequence context initiates with alanine instead of glycine as residue 50, reducing the number of SGXG sequence motifs in the protein from two to one. Expression of this variant syndecan-1 in Madin-Darby canine kidney or MOLT-4 cells yielded a recombinant proteoglycan with a reduced number and clustering of the heparan sulfate chains. Both the conversions of Ala50 and of Lys53 into glycine enhanced the heparan sulfate substitution of the variant protein. These findings support the concept that serine-glycine dipeptide signals for glycosaminoglycan/heparan sulfate synthesis depend on sequence context (Zhang, L., David, G., and Esko, J. D. (1995) J. Biol. Chem. 270, 27127-27135) and imply that alternative splicing mechanisms may in part control the molecular polymorphism of syndecan-1 and, therefore, the efficiency and versatility of this protein in its co-receptor functions.
Romarís
M
M
Laboratory for Glycobiology and Developmental Genetics, Center for Human Genetics, University of Leuven and Flanders Interuniversity Institute for Biotechnology, B-3000 Leuven, Belgium.
Coomans
C
C
Ceulemans
H
H
Bruystens
A M
AM
Vekemans
S
S
David
G
G
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D019765:Chondroitin ABC Lyase / Q000378:metabolism; D004285:Dogs; D006497:Heparan Sulfate / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D011133:Polysaccharide-Lyases / Q000378:metabolism; D011509:Proteoglycans / Q000737:chemistry / Q000235:genetics*; D011994:Recombinant Proteins / Q000096:biosynthesis; D013329:Structure-Activity Relationship; D053668:Syndecan-1; D053667:Syndecans; D014162:Transfection
D019765:Chondroitin ABC Lyase; D006497:Heparan Sulfate; D008562:Membrane Glycoproteins; D011133:Polysaccharide-Lyases; D011509:Proteoglycans; D011994:Recombinant Proteins; D053668:Syndecan-1; D053667:Syndecans; C508242:Sdc1 protein, mouse; C021349:heparitinsulfate lyase