Glycoproteins and glycolipids are primarily expressed at the cell surface of eukaryotic cells. Synthesis, intracellular sorting and transport of them is a major function of the endomembrane system. Although each of the various organelles of the endomembrane system is defined by a unique protein and lipid composition, these compartments are functionally connected by transport vesicles. Anterograde flow of material from the endoplasmic reticulum (ER) via the Golgi to the cell surface and retrograde flow of material from the cell surface towards endosomes/lysosomes, the Golgi and the ER occur simultaneously. It is, therefore, of particular importance that these processes are tightly regulated. Here we discuss molecular mechanisms of how transport vesicles may mediate protein and lipid sorting, thereby maintaining the integrity of the various organelles of the endomembrane system.
IgA nephropathy is a disease characterized by IgA deposits in the renal glomerular mesangium, quite frequently occurring as primary glomerulonephritis and in about 40% of patients in Japan, develops into renal failure within 20 years. The mechanism for the deposition of IgA is still unclear, although the IgA immune complex (IgA-IC) has been detected in glomerular deposits and serum of patients with IgA nephropathy. IgA deposits being a prominent feature of the disease, definite diagnosis can be made by renal biopsy. Considerable study has been undertaken to identify the specific antigen for IgA-IC. The selective deposition of the IgA1 subclass in IgA nephropathy has been reported and structural disorder of the IgA1molecule appears to be a likely explanation for selective deposition. Characteristic structural differences in the two subclasses, IgA1 and IgA2, were examined in the hinge region of the IgA1 subclass which contains a mucin-like structure having O-linked oligosaccharides. The aberrant sugar chain of IgA1 from IgA nephropathy patients has been studied extensively. In this minireview, the structures and functions of mucin-type oligosaccharides in the IgA1 hinge region are summarized and possible involvement in the pathogenesis of this disease is discussed.
Today, hyaluronan (hyaluronic acid) is known to be a polysaccharide widely present in most vertebrate tissues and in the capsule of certain streptococci strains. This macromolecule has further been used in various medical applications such as a supplement in the synovium of osteoarthritic joints, and its impotance is increasing yearly. Hyaluronan is a major component of extracellular matrix, especially in the tissues show high concentration in the molecule coinciding with periods of rapid cell proliferation and migration during embryogenesis. The interaction of hyaluronan with hyaluronan-binding protein and cell-surface receptors dynamically regulates many aspects of cell behavior such as cell adhesion, migration, and differentiation. Furthermore, this ubiquitous macromolecule is involved in many biological processes of morphogenesis, regeneration, wound healing, tumor invasion and cancer metastasis. On the other hand, trials to elucidate the hyaluronan biosynthetic mechanism and to identify a hyaluronan synthase have also been carried out as the main subject of hyaluronan research for past more than 10 years. Identification and molecular cloning of the hyaluronan synthase would shed new light upon questions of hyaluronan research. Recently, we and several other groups have succeeded in the molecular cloning of the prokaryotic and eukaryotic hyaluronan synthases, thereby the elucidation of hyaluronan biosynthetic mechanism and its biological functions are rapidly developing. This review highlights recent topics of hyaluronan synthase and points out the problems encountered in hyaluronan research. Finally, we will mention applications of hyaluronan synthase gene for elucidating the physiological functions of hyaluronan and clinical usage therefore.