title: A novel glycerophosphodiester phosphodiesterase, GDE5, controls skeletal muscle development via a non-enzymatic mechanism.
abstract: Mammalian glycerophosphodiester phosphodiesterases (GP-PDEs) have been identified recently and shown to be implicated in several physiological functions. This study isolated a novel GP-PDE, GDE5, and showed that GDE5 selectively hydrolyzes glycerophosphocholine (GroPCho) and controls skeletal muscle development. We show that GDE5 expression was reduced in atrophied skeletal muscles in mice and that decreasing GDE5 abundance promoted myoblastic differentiation, suggesting that decreased GDE5 expression has a counter-regulatory effect on the progression of skeletal muscle atrophy. Forced expression of full-length GDE5 in cultured myoblasts suppressed myogenic differentiation. Unexpectedly, a truncated GDE5 construct (GDE5DeltaC471), which contained a GP-PDE sequence identified in other GP-PDEs but lacked GroPCho phosphodiesterase activity, showed a similar inhibitory effect. Furthermore, transgenic mice specifically expressing GDE5DeltaC471 in skeletal muscle showed less skeletal muscle mass, especially type II fiber-rich muscle. These results indicate that GDE5 negatively regulates skeletal muscle development even without GroPCho phosphodiesterase activity, providing novel insight into the biological significance of mammalian GP-PDE function in a non-enzymatic mechanism.
authors.affiliation: Department of Molecular and Applied Bioscience, Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima 739-8528, Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Okazaki
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Ohshima
authors.forename: Ikumi
authors.initials: I
authors.lastname: Yoshizawa
authors.forename: Yasutomi
authors.initials: Y
authors.lastname: Kamei
authors.forename: Stefania
authors.initials: S
authors.lastname: Mariggiò
authors.forename: Keiko
authors.initials: K
authors.lastname: Okamoto
authors.forename: Masahiro
authors.initials: M
authors.lastname: Maeda
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Nogusa
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Fujioka
authors.forename: Takashi
authors.initials: T
authors.lastname: Izumi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Shiro
authors.forename: Masanobu
authors.initials: M
authors.lastname: Wada
authors.forename: Norihisa
authors.initials: N
authors.lastname: Kato
authors.forename: Daniela
authors.initials: D
authors.lastname: Corda
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Yanaka
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D003001:Cloning, Molecular; D019295:Computational Biology; D018076:DNA, Complementary / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D024510:Muscle Development; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development*; D009133:Muscular Atrophy / Q000201:enzymology / Q000235:genetics; D010727:Phosphoric Diester Hydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats
chemical_list: D018076:DNA, Complementary; D012333:RNA, Messenger; D010727:Phosphoric Diester Hydrolases; C038133:glycerophosphodiester phosphodiesterase