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Consequences of MEGF10 deficiency on myoblast function and Notch1 interactions

Title
Consequences of MEGF10 deficiency on myoblast function and Notch1 interactions
Authors
Saha, MadhurimaMitsuhashi, SatomiJones, Michael D.Manko, KelseyReddy, Hemakumar M.Bruels, Christine C.Cho, Kyung-AhPacak, Christina A.Draper, IsabelleKang, Peter B.
Ewha Authors
조경아
SCOPUS Author ID
조경아scopus
Issue Date
2017
Journal Title
HUMAN MOLECULAR GENETICS
ISSN
0964-6906JCR Link1460-2083JCR Link
Citation
vol. 26, no. 15, pp. 2984 - 3000
Publisher
OXFORD UNIV PRESS
Indexed
SCI; SCIE; SCOPUS WOS
Abstract
Mutations in MEGF10 cause early onset myopathy, areflexia, respiratory distress, and dysphagia (EMARDD), a rare congenital muscle disease, but the pathogenic mechanisms remain largely unknown. We demonstrate that short hairpin RNA (shRNA)-mediated knockdown of Megf10, as well as overexpression of the pathogenic human p.C774R mutation, leads to impaired proliferation and migration of C2C12 cells. Myoblasts from Megf10(-/-) mice and Megf10(-/-)/mdx double knockout (dko) mice also show impaired proliferation and migration compared to myoblasts from wild type and mdx mice, whereas the dko mice show histological abnormalities that are not observed in either single mutant mouse. Cell proliferation and migration are known to be regulated by the Notch receptor, which plays an essential role in myogenesis. Reciprocal co-immunoprecipitation studies show that Megf10 and Notch1 interact via their respective intracellular domains. These interactions are impaired by the pathogenic p.C774Rmutation. Megf10 regulation of myoblast function appears to be mediated at least in part via interactions with key components of the Notch signaling pathway, and defects in these interactions may contribute to the pathogenesis of EMARDD.
DOI
10.1093/hmg/ddx189
Appears in Collections:
연구기관 > 의과학연구소 > Journal papers
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