2. Academic Validation
  3. Cell endogenous activities of fukutin and FKRP coexist with the ribitol xylosyltransferase, TMEM5

Cell endogenous activities of fukutin and FKRP coexist with the ribitol xylosyltransferase, TMEM5

  • Biochem Biophys Res Commun. 2018 Mar 18;497(4):1025-1030. doi: 10.1016/j.bbrc.2018.02.162.
Ryuta Nishihara 1,  Kazuhiro Kobayashi 1,  Rieko Imae 2,  Hiroki Tsumoto 3,  Hiroshi Manya 2,  Mamoru Mizuno 4,  Motoi Kanagawa 1,  Tamao Endo 2,  Tatsushi Toda 5
Affiliations

Affiliations

  • 1 Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-chou, Chuo-ku, Kobe 650-0017, Japan.
  • 2 Molecular Glycobiology, Research Team for Mechanism of Aging, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo 173-0015, Japan.
  • 3 Proteome Research, Research Team for Mechanism of Aging, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo 173-0015, Japan.
  • 4 Laboratory of Glyco-organic Chemistry, The Noguchi Institute, Itabashi, Tokyo 173-0003, Japan.
  • 5 Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-chou, Chuo-ku, Kobe 650-0017, Japan; Department of Neurology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Electronic address: [email protected].
PMID: 29477842 DOI: 10.1016/j.bbrc.2018.02.162
Abstract

Dystroglycanopathies are a group of muscular dystrophies that are caused by abnormal glycosylation of dystroglycan; currently 18 causative genes are known. Functions of the dystroglycanopathy genes fukutin, fukutin-related protein (FKRP), and transmembrane protein 5 (TMEM5) were most recently identified; fukutin and FKRP are ribitol-phosphate transferases and TMEM5 is a ribitol xylosyltransferase. In this study, we show that fukutin, FKRP, and TMEM5 form a complex while maintaining each of their Enzyme activities. Immunoprecipitation and immunofluorescence experiments demonstrated protein interactions between these 3 proteins. A protein complex consisting of endogenous fukutin and FKRP, and exogenously expressed TMEM5 exerts activities of each Enzyme. Our data showed for the first time that endogenous fukutin and FKRP Enzyme activities coexist with TMEM5 Enzyme activity, and suggest the possibility that formation of this Enzyme complex may contribute to specific and prompt biosynthesis of glycans that are required for dystroglycan function.

Keywords

FKRP; Fukutin; O-mannosyl glycan; Protein complex; TMEM5; α-Dystroglycan.

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