TRPM7 regulates myosin IIA filament stability and protein localization by heavy chain phosphorylation.

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Publication year
2008Source
Journal of Molecular Biology, 378, 4, (2008), pp. 790-803ISSN
Publication type
Article / Letter to editor

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Organization
Tumorimmunology
Paediatrics - OUD tm 2017
CMBI
Former Organization
Bioinformatics (umcn)
Journal title
Journal of Molecular Biology
Volume
vol. 378
Issue
iss. 4
Page start
p. 790
Page end
p. 803
Subject
IGMD 8: Mitochondrial medicine; NCMLS 1: Immunity, infection and tissue repair; NCMLS 2: Immune Regulation; NCMLS 2: Metabolism, transport and motion; ONCOL 2: Age-related aspects of cancer; ONCOL 3: Translational research; UMCN 1.4: Immunotherapy, gene therapy and transplantation; UMCN 5.3: Cellular energy metabolismAbstract
Deregulation of myosin II-based contractility contributes to the pathogenesis of human diseases, such as cancer, which underscores the necessity for tight spatial and temporal control of myosin II activity. Recently, we demonstrated that activation of the mammalian alpha-kinase TRPM7 inhibits myosin II-based contractility in a Ca(2+)- and kinase-dependent manner. However, the molecular mechanism is poorly defined. Here, we demonstrate that TRPM7 phosphorylates the COOH-termini of both mouse and human myosin IIA heavy chains--the COOH-terminus being a region that is critical for filament stability. Phosphorylated residues were mapped to Thr1800, Ser1803 and Ser1808. Mutation of these residues to alanine and that to aspartic acid lead to an increase and a decrease, respectively, in myosin IIA incorporation into the actomyosin cytoskeleton and accordingly affect subcellular localization. In conclusion, our data demonstrate that TRPM7 regulates myosin IIA filament stability and localization by phosphorylating a short stretch of amino acids within the alpha-helical tail of the myosin IIA heavy chain.
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- Academic publications [227881]
- Electronic publications [107344]
- Faculty of Medical Sciences [86219]
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