福库亭和FKRP的细胞内源性活性与核糖醇木糖基转移酶TMEM5共存。

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

作者信息

Nishihara Ryuta, Kobayashi Kazuhiro, Imae Rieko, Tsumoto Hiroki, Manya Hiroshi, Mizuno Mamoru, Kanagawa Motoi, Endo Tamao, Toda Tatsushi

机构信息

Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-chou, Chuo-ku, Kobe 650-0017, Japan.

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.

出版信息

Biochem Biophys Res Commun. 2018 Mar 18;497(4):1025-1030. doi: 10.1016/j.bbrc.2018.02.162.

DOI:10.1016/j.bbrc.2018.02.162

PMID:29477842

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.

摘要

肌聚糖病是一组由肌聚糖糖基化异常引起的肌肉营养不良症；目前已知有18个致病基因。最近确定了肌聚糖病相关基因福金、福金相关蛋白（FKRP）和跨膜蛋白5（TMEM5）的功能；福金和FKRP是核糖醇磷酸转移酶，TMEM5是核糖醇木糖基转移酶。在本研究中，我们发现福金、FKRP和TMEM5形成了一个复合物，同时保持各自的酶活性。免疫沉淀和免疫荧光实验证明了这三种蛋白质之间的相互作用。由内源性福金和FKRP以及外源性表达的TMEM5组成的蛋白质复合物发挥着每种酶的活性。我们的数据首次表明内源性福金和FKRP的酶活性与TMEM5的酶活性共存，并提示这种酶复合物的形成可能有助于肌聚糖功能所需聚糖的特异性和快速生物合成。