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 nucleot ides of the third exon of the syndecan-1 gene. The corresponding message is rare. The alternative splice respects the reading frame and deletes 44 ami no acids from the protein, joining the S(45)GS(47)GT 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 moti fs 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 proteoglyc an with a reduced number and clustering of the heparan sulfate chains, Both the conversions of Ala(50) and of Lys(53) into glycine enhanced the hepara n sulfate substitution of the variant protein. These findings support the c oncept that serine glycine dipeptide signals for glycosaminoglycan/heparan sulfate synthesis depend on sequence context (Zhang, L., David, G.., and Es ko, J. D. (1995) J. Biol. Chem, 270, 27127-27135) and imply that alternativ e splicing mechanisms may in part control the molecular polymorphism of syn decan-1 and, therefore, the efficiency and versatility of this protein in i ts co-receptor functions.