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2014 Fiscal Year Final Research Report

Molecular characterization of a HECT-type E3 ubiquitin ligase that is encoded in the WWP1 gene responsible for chicken muscular dystrophy.

Research Project

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Project/Area Number 24500472
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurophysiology and muscle physiology
Research InstitutionNational Center of Neurology and Psychiatry

Principal Investigator

IMAMURA Michihiro  独立行政法人国立精神・神経医療研究センター, 神経研究所 遺伝子疾患治療研究部, 室長 (80221787)

Co-Investigator(Kenkyū-buntansha) TAKEDA Shin'ichi  独立行政法人国立精神・神経医療研究センター神経研究所, 遺伝子疾患治療研究部, 部長 (90171644)
Project Period (FY) 2012-04-01 – 2015-03-31
Keywords筋ジストロフィー / 実験動物 / 遺伝子疾患 / WWP1 E3 ユビキチンリガーゼ / タンパク質分解
Outline of Final Research Achievements

The R441Q missense mutation in the WWP1 protein was reported as the most promising candidate responsible for chicken muscular dystrophy (MD). We generated an antibody against WWP1, and characterized WWP1 protein expression in skeletal muscles in vivo and in vitro. In wild-type skeletal muscle, WWP1 was detected as an approximately 130-kDa protein and localized to the sarcolemma, sarcoplasmic reticulum, mitochondria, as well as in a part of the nucleus, whereas it was markedly degraded and absent from the sarcolemma in MD muscle. These changes were already observed in MD chickens in the pre-pathological stage. In vitro expression analysis demonstrated significant degradation of mutant but not wild-type WWP1, specifically in myogenic cells. Our study revealed that the R441Q missense mutation in the WWP1 protein causes its degradation as well as loss of its sarcolemmal localization, which are hence implicated in the pathogenesis of chicken MD.

Free Research Field

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Published: 2016-06-03  

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