Calmodulin Methyltransferase Is Required for Growth, Muscle Strength, Somatosensory Development and Brain Function

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Calmodulin (CaM) is a highly abundant, ubiquitous, small protein, which plays a major role in the transmission of calcium signals to target proteins in eukaryotes. Hundreds of CaM targets are known, and their respective cellular functions include signaling, metabolism, cytoskeletal regulation, and ion channel regulation, to name but a few. CaM is frequently modified after translation, including frequently trimethylation at a single amino acid, however, the role of this methylation is not known. Human patients with a homozygous deletion of the gene that methylates CaM, CaM-KMT, are known, but they also have a deletion of additional genes. Thus, to study the role of CaM–KMT, we produced a mouse model in which CaM-KMT is the only deleted gene, with the deletion constructed as in the human patients. The model proved to reveal the function of methylation of CaM, since CaM was found to be non-methylated and the methylation of CaM found to be important in growth, muscle strength, somatosensory development and brain function. The current study also has clinical implications for human patients. Patients presenting slow growth and muscle weakness that could result from a mitochondrial impairment and mental retardation should be considered for sequence analysis of the CaM KMT gene.

Vyšlo v časopise: Calmodulin Methyltransferase Is Required for Growth, Muscle Strength, Somatosensory Development and Brain Function. PLoS Genet 11(8): e32767. doi:10.1371/journal.pgen.1005388
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005388

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