A novel glycerophosphodiester phosphodiesterase, GDE5, controls skeletal muscle development via a non-enzymatic mechanism

Yuri Okazaki, Noriyasu Ohshima, Ikumi Yoshizawa, Yasutomi Kamei, Stefania Mariggiò, Keiko Okamoto, Masahiro Maeda, Yoshihito Nogusa, Yuichiro Fujioka, Takashi Izumi, Yoshihiro Ogawa, Yoshitsugu Shiro, Masanobu Wada, Norihisa Kato, Daniela Corda, Noriyuki Yanaka

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

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 (GDE5 Δ C471), 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 GDE5 Δ C471 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.

Original languageEnglish
Pages (from-to)27652-27663
Number of pages12
JournalJournal of Biological Chemistry
Volume285
Issue number36
DOIs
Publication statusPublished - Sep 3 2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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