The extracellular matrix provides scaffolding and stability to tissues and organs. It also is interactive with the component cells, providing information which affects their behavior. Laminin is a major constituent of a specialized form of the extracellular matrix, the basal lamina. In adult tissues and organs, cells tightly adhere to a basal lamina while in embryonic tissues the basal laminae are believed to help orchestrate developmental processes. Cells respond to the information encoded by laminin by recognizing its structural features. A comprehensive picture of the molecular anatomy of laminin is available, including its overall molecular structure, its content of polypeptide subunits and amino acid sequences, its carbohydrate composition and the structures of its N-linked oligosaccharides. Both the protein and carbohydrate moieties are implicated in cellular recognition and cellular responses to laminin. We review the current state of knowledge about laminin structure and biological activities, especially focusing upon the putative roles of laminin carbohydrates in mediating cellular responses to laminin. Several models of cell surface interaction with laminin are proposed. As our knowledge of these interactions expands, further refinement of the models should provide better definition of the mechanisms by which laminin carbohydrates are able to prompt cell responses.
Human blood group antigens on red cells can be broadly classified into carbohydrates and proteins. The former category includes ABH, Lewis (Le), Ii, and P-related antigens, and the latter category is represented in this minireview by the Duffy antigens (Fya and Fyb), and the M and N antigens carried on glycophorin A. The ABH and Ii antigens are located on the polylactosaminoglycans of glycoproteins Band 3 and Band 4.5, and on polyglycosylceramides. The Lea, Leb and the P-related antigens are associated only with glycosphingolipids. These carbohydrate-dependent antigens are expressed not only on red cells, but they are also detected on various epithelial tissues, organs, and secretions. Some of them are tumor-associated as their expressions on certain malignant tissues are incompatible with the blood groups of the cancer patients. The Duffy antigens and glycophorin A are erythroid specific. They have been identified as separate ligands to which the merozoites of Plasmodium knowlesi (or P. vivax) and Plasmodium falciparum attach respectively at the asexual stage of the life cycle of these malarial parasites.
The covalent addition of lipids to the protein core of heparan sulfate proteoglycans provides novel molecular bonds between these gene products and the plasma membrane. Glypiation of proteoglycans is involved in apical sorting, membrane targeting and it provides a mechanism for rapid enzymatic release of surface proteoglycans. Fatty acylation of proteoglycans mediates hydrophobic interactions and possibly receptor-mediated binding, it can provide a novel mechanism for intracellular proteoglycan/proteoglycan interaction and may play a direct role in turnover. Identification of the fine structural requirements and complex enzymatic machinery involved in lipid anchoring will establish the functional sigmficance for these novel post-translational modifications of proteoglycans.
CD44 is a polymorphic family of cell surface glycoproteins expressed by a variety of cells. The CD44 proteins mediate cell-cell and cell-substrate adhesion as well as lymphocyte activation. Here we review the recent isolation and characterization of cDNAs encoding two CD44 proteins, CD44H and CD44E. CD44H is an 80-90kD glycoprotein expressed by cells of both mesodermal and neuro-ectodermal origin. Adhesion studies have shown that CD44H specifically binds hyaluronan. This observation, in conjunction with the finding that the hamster CD44H protein reacts with a monoclonal antibody directed against the hamster hyaluronan receptor indicates that CD44H and the hyaluronan receptor are the same molecule. CD44E is a 150kD glycoprotein expressed by a subset of epithelial cells and contains an additional segment of 134 amino acids intercalated within the extracellular domain of CD44H. Adhesion studies indicate that unlike CD44H, CD44E does not mediate attachment to surface bound hyaluronate.
Considerable information has been obtained regarding the intermediates and the order of biosynthesis of the glycosaminoglycan portion of proteochondroitin and in its sulfation. Nevertheless, the relationship of these two steps have not been clearly defined. Work in several laboratories, including our own, have indicated a pattern which strongly suggests that sulfation ordinarily takes place together with polymerization in a single Golgi site, and with close interrelationships of sulfation, polymer elongation, and polymer termination. These interactions could contribute to the control of specific variations in location and type of sulfation that might in turn direct specific functions of the proteochondroitin sulfate.
The mode of action of the sulfatases in the glycosaminoglycan metabolism is briefly reviewed. The evidences so far obtained suggest that there are three pathways of degradation of glycosaminoglycans involving several specific sulfatases with distinct modes of action. In mammals, and possibly in other vertebrates, the sulfatases act on a sequential order in concert with sugar hydrolases, removing sulfates from the nonreducing ends of the molecules in each cycle of degradation. In invertebrates, the sulfatases act directly upon the polymer producing extensive desulfation without need of concomitant depolymerization which takes place only on a second stage, by action of the sugar hydrolases. Finally, in bacteria, the sulfatases act only upon sulfated disaccharides and monosaccharides formed from the glycosaminoglycans by action of eliminases and glycuronidases. The biological role of the sulfatases on the recycling of sugars and sulfate is discussed.
A major class of glycoproteins found on the surfaces of growing axons are members of the immunoglobulin (Ig) super-family of proteins that contain both Ig-like domains and fibronectin type III-like domains. The pattern of expression of these proteins during development combined with in vitro studies of their function, suggest that these proteins have a role in regulating axonal growth patterns and guidance by modulating cell surface adhesivity. Recent in vivo studies suggest that at least one mechanism used to modulate axonal adhesivity involves regulation of the polysialic acid content of one member of this family, NCAM. The increasing diversity of this family and the discovery of multiple isoforms of these proteins suggest that other mechanisms may also exist for regulating axonal growth and guidance.