title: Ectodomain shedding of neuroglycan C, a brain-specific chondroitin sulfate proteoglycan, by TIMP-2- and TIMP-3-sensitive proteolysis.
abstract: Neuroglycan C (NGC) is a transmembrane-type of chondroitin sulfate proteoglycan with an epidermal growth factor (EGF)-like module that is exclusively expressed in the CNS. Because ectodomain shedding is a common processing step for many transmembrane proteins, we examined whether NGC was subjected to proteolytic cleavage. Western blotting demonstrated the occurrence of a soluble form of NGC with a 75 kDa core glycoprotein in the soluble fraction of the young rat cerebrum. In contrast, full-length NGC with a 120 kDa core glycoprotein and its cytoplasmic fragment with a molecular size of 35 kDa could be detected in the membrane fraction. The soluble form of NGC was also detectable in culture media of fetal rat neurons, and the full-length form existed in cell layers. The amount of the soluble form in culture media was decreased by adding a physiological protease inhibitor such as a tissue inhibitor of metalloproteinase (TIMP)-2 or TIMP-3, but not by adding TIMP-1. Both EGF-like and neurite outgrowth-promoting activity of the NGC ectodomain may be regulated by this proteolytic processing.
authors.affiliation: Department of Perinatology and Neuroglycoscience, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi, JapanDepartment of Neurochemistry, Nagoya University Graduate School of Medicine, Nagoya, JapanDepartment of Environmental Health, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Shuo
authors.affiliation: Department of Perinatology and Neuroglycoscience, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi, JapanDepartment of Neurochemistry, Nagoya University Graduate School of Medicine, Nagoya, JapanDepartment of Environmental Health, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Aono
authors.affiliation: Department of Perinatology and Neuroglycoscience, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi, JapanDepartment of Neurochemistry, Nagoya University Graduate School of Medicine, Nagoya, JapanDepartment of Environmental Health, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Nakanishi
authors.affiliation: Department of Perinatology and Neuroglycoscience, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi, JapanDepartment of Neurochemistry, Nagoya University Graduate School of Medicine, Nagoya, JapanDepartment of Environmental Health, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Tokita
authors.affiliation: Department of Perinatology and Neuroglycoscience, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi, JapanDepartment of Neurochemistry, Nagoya University Graduate School of Medicine, Nagoya, JapanDepartment of Environmental Health, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kuroda
authors.affiliation: Department of Perinatology and Neuroglycoscience, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi, JapanDepartment of Neurochemistry, Nagoya University Graduate School of Medicine, Nagoya, JapanDepartment of Environmental Health, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
authors.forename: Michiru
authors.initials: M
authors.lastname: Ida
authors.affiliation: Department of Perinatology and Neuroglycoscience, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi, JapanDepartment of Neurochemistry, Nagoya University Graduate School of Medicine, Nagoya, JapanDepartment of Environmental Health, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
authors.forename: Fumiko
authors.initials: F
authors.lastname: Matsui
authors.affiliation: Department of Perinatology and Neuroglycoscience, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi, JapanDepartment of Neurochemistry, Nagoya University Graduate School of Medicine, Nagoya, JapanDepartment of Environmental Health, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
authors.forename: Hiroyo
authors.initials: H
authors.lastname: Maruyama
authors.affiliation: Department of Perinatology and Neuroglycoscience, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi, JapanDepartment of Neurochemistry, Nagoya University Graduate School of Medicine, Nagoya, JapanDepartment of Environmental Health, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kaji
authors.affiliation: Department of Perinatology and Neuroglycoscience, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi, JapanDepartment of Neurochemistry, Nagoya University Graduate School of Medicine, Nagoya, JapanDepartment of Environmental Health, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Oohira
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000494:pharmacology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004151:Dipeptides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006877:Hydroxamic Acids / Q000494:pharmacology; D047468:Immunoprecipitation / Q000379:methods; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D008970:Molecular Weight; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology*; D011509:Proteoglycans / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000037:antagonists & inhibitors*; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000037:antagonists & inhibitors*
chemical_list: D000906:Antibodies; C485738:Cspg5 protein, rat; D004151:Dipeptides; D006877:Hydroxamic Acids; D008565:Membrane Proteins; C092152:N-((2-(hydroxyaminocarbonyl)methyl)-4-methylpentanoyl)-3-(2'-naphthyl)alanylalanine, 2-aminoethylamide; D011480:Protease Inhibitors; D011509:Proteoglycans; D019717:Tissue Inhibitor of Metalloproteinase-3; D019716:Tissue Inhibitor of Metalloproteinase-2