Chondroitin sulfate (CS) and dermatan sulfate (DS) are widely distributed as sulfated glycosaminoglycan side chains of proteoglycans in extracellular matrices and at cell surfaces. Increasing evidence suggests the importance of CS/DS chains in several biological functions. For example, in the development and regeneration of the central nervous system, they have apparently contradictory roles as neuritogenic molecules and as major inhibitors of axonal pathfinding and regeneration. These functions are closely associated with the characteristic sulfated structures embedded in the CS/DS chains, and are exerted through distinct molecular mechanisms, at least in part, by specific interactions between CS/DS chains and heparin-binding growth factors.
Heparan sulfate proteoglycans (HSPGs) are complex glycoproteins present ubiquitously at the cell surface and in the extracellular matrix. Heparan sulfate (HS) and HSPGs interact with a variety of growth factors, morphogens, extracellular matrix (ECM) proteins and proteases and thus play essential roles in controlling cell differentiation, tissue morphogenesis and homeostasis. The importance of HS and HSPGs has been highlighted by the findings that a number of human genetic disorders are associated with mutations in genes encoding for HSPGs or HS biosynthetic enzymes. The HS mediated interactions are often dependent on specific HS structures that arise from differential sulfation modifications to the sugar backbone during biosynthesis. The fine structure of HS varies tissue specifically, during development and in disease conditions but the regulation of HS biosynthesis is still not fully understood. Recent studies using genetic model organisms together with cell biological and biochemical approaches have indicated specific roles for heparan sulfotransferases in defined developmental pathways emphasizing the importance of specific HS structures during development.
Siglecs are a family of immunoglobulin superfamily proteins recognizing glycans that contain sialic acid. Most CD33-related Siglecs were thought to recognize sialylated glycans rather promiscuously, while other, more evolutionarily conserved Siglecs recognize glycans with high specificity. However, recent studies have revealed unexpectedly specific glycan recognition by some of the CD33-related Siglecs, such as human Siglec-8 and mouse Siglec-F. Studies of CD22/Siglec-2 and myelin-associated glycoprotein/Siglec-4 suggest that both cis- and trans-ligands may be involved in regulation of Siglec functions. Preferential recognition of specific glycans by some CD33-related Siglecs may imply the presence of specific trans-ligands, and this possibility should be tested by a search for such ligands and biological assays using cellular and/or animal models.
Recently, it has become clear that glycosyltransferases (GTs) form complexes in various manners. Some GTs can associate by themselves to form homodimers or homooligomers, while other GTs can associate with non-GT proteins to form hetero-oligomers. The biological significance of the complex formation is diverse; activation or stabilization of catalytic activities, alteration of substrate specificities, economical biosynthesis of glycans, localization and transport in the ER or the Golgi apparatus, modification of catalytic activities via certain effector proteins, and so on. Here, I will review a number of studies on GT complexes.