Abstract

Oral Sessions

Day 1: Wednesday, May 18　16:05-16:25　Room A (Orbit Hall)

1A-O1-1605　　PDF

Identification of a post-translational modification with ribitol-phosphate and its defect in muscular dystrophy

(¹Osaka MCHRI, ²Kobe Univ., ³TMIG, ⁴RIKEN, ⁵Hokkaido Univ., ⁶Noguchi Inst.)
^oMichiko Tajiri¹, Motoi Kanagawa², Kazuhiro Kobayashi², Hiroshi Manya³, Atsushi Kuga², Yoshiki Yamaguchi⁴, Keiko Akasaka-manya³, Jun-ichi Furukawa⁵, Mamoru Mizuno⁶, Hiroko Kawakami⁶, Yasuro Shinohara⁵, Tamao Endo³, Tatsushi Toda², Yoshinao Wada¹

α-Dystroglycan (α-DG) is a receptor for matrix and synaptic proteins that causes muscular dystrophy and lissencephaly upon its abnormal glycosylation (α-dystroglycanopathies). Here we identified the previously unknown glycan unit ribitol 5-phosphate (Rbo5P), a phosphoric ester of pentose alcohol, in α-DG. Rbo5P forms a tandem repeat and functions as a scaffold for the formation of the ligand-binding moiety. We found the enzyme activities of three major α-dystroglycanopathy-causing proteins to be involved in the synthesis of tandem Rbo5P. Isoprenoid synthase domain-containing (ISPD) is cytidine diphosphate ribitol (CDP-Rbo) synthase. Fukutin and fukutin-related protein are sequentially acting Rbo5P transferases that use CDP-Rbo.