Integral Membrane Heparan Sulfate Proteoglycans

Heparan sulfate is a regulatory polysaccharide. It modulates specific growth factor-receptor interactions, accelerates the formation of specific proteinase-proteinase inhibitor complexes, and mediates interactions of the cell surface with several enzymes and structural proteins. It abounds on the surfaces of embryonic cells, respecting or outlining morphogenetic rather than histological boundaries. This cell surface-associated heparan sulfate is implanted on specific integral membrane proteins, which together constitute two novel molecular families. The first family includes four syndecan-like integral membrane proteoglycans (SLIPS), with core proteins that span the membrane and shared sequence motifs in highly conserved cytoplasmic domains. The second is made up by two or more glypican-related integral membrane proteoglycans (GRIPS) that are linked to the cell surface via glycosyl phosphatidylinositol. These proteoglycans show differential expression and turnover patterns, prevailing in distinct cell types, membrane domains, and endocytotic machineries, and are subject to strict developmental controls. This suggests that each of these cell surface proteoglycans functions in a specific context, and that these functions pertain to the transduction of signals that emanate from the continuous interplay between matrix components, growth factors, and proteinases. Caution: beware of loose GRIPS and SLIPS on unsteady cell surfaces.