Characterization and functional studies of a FYVE domain-containing phosphatase in C. elegans.
The myotubularin (MTM) enzymes are phosphatidylinositol 3-phosphate (PI3P) and phosphatidylinositol 3,5-bisphosphate phosphatases. Mutation of MTM1, the founder member of this family, is responsible for X-linked myotubular myopathy in humans. Here, we have isolated and characterized a Caenorhabditis elegans homology of the enzymes designated ceMTM3. ceMTM3 preferably dephosphorylates PI3P and contains a FYVE lipid-binding domain at its C-terminus which binds PI3P. Immunoblotting analyses revealed that the enzyme is expressed during the early development and adulthood of the animal. Immunofluorescent staining revealed predominant expression of the enzyme in eggs and muscles. Knockdown of the enzyme by using feeding-based RNA interference resulted in an increased level of PI3P and caused severe impairment of body movement of the worms at their post-reproductive ages and significantly shortened their lifespan. This study thus reveals an important role of the MTM phosphatases in maintaining muscle function, which may have clinical implications in prevention and treatment of sarcopenia.
Ma
Junfeng
J
Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA.
Zeng
Fenghua
F
Ho
Wanting Tina
WT
Teng
Lirong
L
Li
Qingshan
Q
Fu
Xueqi
X
Zhao
Zhizhuang Joe
ZJ
D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry* / Q000378:metabolism*; D003001:Cloning, Molecular; D008124:Locomotion; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000737:chemistry* / Q000378:metabolism*; D034622:RNA Interference; D013379:Substrate Specificity; D016019:Survival Analysis
D029742:Caenorhabditis elegans Proteins; D018129:Phosphatidylinositol Phosphates; C060974:phosphatidylinositol 3,4,5-triphosphate; D054558:Protein Tyrosine Phosphatases, Non-Receptor; C532246:mtm-3 protein, C elegans