Molecular polymorphism of a cell surface proteoglycan: distinct structures on simple and stratified epithelia.

Abstract

Epithelial cells are organized into either a single layer (simple epithelia) or multiple layers (stratified epithelia). Maintenance of these cellular organizations requires distinct adhesive mechanisms involving many cell surface molecules. One such molecule is a cell surface proteoglycan, named syndecan, that contains both heparan sulfate and chondroitin sulfate chains. This proteoglycan binds cells to fibrillar collagens and fibronectin and thus acts as a receptor for interstitial matrix. The proteoglycan is restricted to the basolateral surface of simple epithelial cells, but is located over the entire surface of stratified epithelial cells, even those surfaces not contacting matrix. We now show that the distinct localization in simple and stratified epithelia correlates with a distinct proteoglycan structure. The proteoglycan from simple epithelia (modal molecular size, 160 kDa) is larger than that from stratified epithelia (modal molecular size, 92 kDa), but their core proteins are identical in size and immunoreactivity. The proteoglycan from simple epithelia has more and larger heparan sulfate and chondroitin sulfate chains than the proteoglycan from stratified epithelia. Thus, the cell surface proteoglycan shows a tissue-specific structural polymorphism due to distinct posttranslational modifications. This polymorphism likely reflects distinct proteoglycan functions in simple and stratified epithelia, potentially meeting the different adhesive requirements of the cells in these different organizations.Epithelial tissues consist of the cells that line the free surfaces of the body. These cells are organized into either of two arrangements: cells in a single layer (simple epithelia) or cells in two or more layers (stratified epithelia). These arrangements reflect the usual functions of these cells, namely transfer of materials across simple epithelia and protection by stratified epithelia. Both of these functions require that the cells adhere to one another and to their underlying extracellular matrix.Several cell surface molecules involved in cell-cell and cell-matrix adhesion on epithelia have been described (see refs. 1-5 Restriction of the proteoglycan to the basolateral cell surface on simple epithelia is consistent with its behavior as a matrix receptor; its localization over the entire cell surface on stratified epithelia is not. This difference raises the possibility that the nature of the proteoglycan in these epithelial types could differ. Therefore, we compared the structure of the cell surface proteoglycan extracted from simple and stratified epithelia, from both tissues and cells in culture, to assess whether its distinct cellular localization correlates with a distinct molecular structure. Part of these data has been published in abstract form (13). MATERIALS AND METHODSCell and Organ Culture. Normal murine mammary gland epithelial cells (passages 13-22) were maintained as described (14). Keratinocytes from newborn mouse skin were isolated and cultured by the method of Hennings et al....

Syndecans: multifunctional cell-surface co-receptors

“…The addition of glycosaminoglycan chains to syndecans is critical, since these provide all of the known extracellular ligand binding sites on syndecans. While there is no evidence for the existence of alternative splicing of syndecan core proteins as a mechanism to generate structural variants, structurally distinct forms of syndecans can be produced as a result of variations in the number, type, length or fine structure of the attached glycosaminoglycans [20][21][22][23].…”

“…Different cell types have been shown to synthesize syndecans with different glycosaminoglycan structures and, in some cases, different functional activities. For example, syndecan-1 molecules produced by simple epithelial cells are modified by more and larger heparan sulphate and chondroitin sulphate chains than syndecan-1 molecules produced by stratified epithelial cells [20]. Heparan sulphate chains on syndecan-1 molecules isolated from different cell lines can also differ in fine structure.…”

Immunohistochemical expression of heparan sulfate correlates with stromal cell proliferation in breast phyllodes tumors

“…[1][2][3] Its primary structure is characterized by repeats of disaccharide units of a uronic acid and a derivative of glucosamine. The biosynthetic process of heparan sulfate is highly complicated whereby it can undergo modifications such as sulfation, epimerization, and acetylation to generate a great structural diversity of heparan sulfate chains.…”

Glycotranscriptome study reveals an enzymatic switch modulating glycosaminoglycan synthesis during B‐cell development and activation

“…These physiological variations proved important both for an optimal early B-cell differentiation and proliferative responses of mature cells. GAGs (and notably syndecan-1) have been shown in other tissues to be differentially branched either with HS chains, then promoting cell adhesion, or with CS chains then promoting cell migration [34][35][36]. Part of the regulation of these properties may be at the level of expression of the core protein of GAGs, since transfected cells overexpressing syndecan-1 or syndecan-4 display increased intercellular adhesion due to the HS chains of syndecan [37].…”