title: Multiple heparan sulfate chains are required for optimal syndecan-1 function.
abstract: Syndecans have three highly conserved sites available for heparan sulfate attachment. To determine if all three sites are required for normal function, a series of mutated syndecans having two, one, or no heparan sulfate chains were expressed in ARH-77 cells. Previously, we demonstrated that expression of wild-type syndecan-1 on these myeloma cells mediates cell-matrix and cell-cell adhesion and inhibits cell invasion into collagen gels. Here we show that to optimally mediate each of these activities, all three sites of heparan sulfate attachment are required. Generally, an increasing loss of syndecan-1 function occurs as the number of heparan sulfate attachment sites decreases. This loss of function is not the result of a decrease in either the total amount of cell surface heparan sulfate or syndecan-1 core protein. In regard to cell invasion, cells expressing syndecan-1 bearing a single heparan sulfate attachment site exhibit a hierarchy of function based upon the position of the site within the core protein; the presence of an available attachment site at serine 47 confers the greatest level of activity, while serine 37 contributes little to syndecan-1 function. However, when all three heparan sulfate chains are present, significantly greater biological activity is observed than is predicted by the sum of the activities occurring when the chains act individually. This synergy provides a functional basis for the evolutionary conservation of the three heparan sulfate attachment sites on syndecans and supports the idea that molecular heterogeneity, which is characteristic of proteoglycans, contributes to their functional diversity.
authors.affiliation: Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
authors.forename: J K
authors.initials: JK
authors.lastname: Langford
authors.forename: M J
authors.initials: MJ
authors.lastname: Stanley
authors.forename: D
authors.initials: D
authors.lastname: Cao
authors.forename: R D
authors.initials: RD
authors.lastname: Sanderson
mesh_terms: D002448:Cell Adhesion; D002460:Cell Line; D003094:Collagen / Q000378:metabolism; D006497:Heparan Sulfate / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D011509:Proteoglycans / Q000378:metabolism*; D017384:Sequence Deletion; D053668:Syndecan-1; D053667:Syndecans
chemical_list: D003094:Collagen; D006497:Heparan Sulfate; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D053668:Syndecan-1; D053667:Syndecans; C508241:SDC1 protein, human