title: Subcellular localization and physiological significance of intracellular mannan-binding protein.
abstract: Mannan-binding protein (MBP) is a C-type mammalian lectin specific for mannose and N-acetylglucosamine. MBP is mainly synthesized in the liver and occurs naturally in two forms, serum MBP (S-MBP) and intracellular MBP (I-MBP). S-MBP activates complement in association with MBP-associated serine proteases via the lectin pathway. Despite our previous study (Mori, K., Kawasaki, T., and Yamashina, I. (1984) Arch. Biochem. Biophys. 232, 223-233), the subcellular localization of I-MBP and its functional implication have not been clarified yet. Here, as an extension of our previous studies, we have demonstrated that the expression of human MBP cDNA reproduces native MBP differentiation of S-MBP and I-MBP in human hepatoma cells. I-MBP shows distinct accumulation in cytoplasmic granules, and is predominantly localized in the endoplasmic reticulum (ER) and involved in COPII vesicle-mediated ER-to-Golgi transport. However, the subcellular localization of either a mutant (C236S/C244S) I-MBP, which lacks carbohydrate-binding activity, or the wild-type I-MBP in tunicamycin-treated cells shows an equally diffuse cytoplasmic distribution, suggesting that the unique accumulation of I-MBP in the ER and COPII vesicles is mediated by an N-glycan-lectin interaction. Furthermore, the binding of I-MBP with glycoprotein intermediates occurs in the ER, which is carbohydrate- and pH-dependent, and is affected by glucose-trimmed high-mannose-type oligosaccharides. These results strongly indicate that I-MBP may function as a cargo transport lectin facilitating ER-to-Golgi traffic in glycoprotein quality control.
authors: Research Center for Glycobiotechnology, Ritsumeikan University, Shiga 525-8577, Japan.
authors: Motohiro
authors: M
authors: Nonaka
authors: Bruce Yong
authors: BY
authors: Ma
authors: Misato
authors: M
authors: Ohtani
authors: Akitsugu
authors: A
authors: Yamamoto
authors: Masayuki
authors: M
authors: Murata
authors: Kiichiro
authors: K
authors: Totani
authors: Yukishige
authors: Y
authors: Ito
authors: Keiko
authors: K
authors: Miwa
authors: Wataru
authors: W
authors: Nogami
authors: Nobuko
authors: N
authors: Kawasaki
authors: Toshisuke
authors: T
authors: Kawasaki
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms; D051907:Lysosomal Membrane Proteins / Q000378:metabolism*; D037601:Mannose-Binding Lectin / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D013347:Subcellular Fractions / Q000378:metabolism; D020349:Surface Plasmon Resonance; D019284:Thapsigargin / Q000378:metabolism; D052118:Lysosomal-Associated Membrane Protein 1
chemical_list: D015699:HIV Envelope Protein gp120; D051907:Lysosomal Membrane Proteins; D037601:Mannose-Binding Lectin; D009844:Oligosaccharides; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; D019284:Thapsigargin; C489116:LAMP1 protein, human; D052118:Lysosomal-Associated Membrane Protein 1