Consequences of MEGF10 deficiency on myoblast function and Notch1 interactions

Human Molecular Genetics
Madhurima SahaPeter B Kang

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.C774R mutation. 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.

References

Feb 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·G BulfieldK J Moore
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Jun 22, 2002·Current Opinion in Genetics & Development·Madeleine Durbeej, Kevin P Campbell
May 4, 2004·Journal of Medical Genetics·D Beltran-Valero de BernabéF Muntoni
Dec 22, 2004·Biotechnology Advances·Grzegorz Bulaj
Jun 21, 2005·Nature Neuroscience·Mototsugu EirakuMineko Kengaku
Aug 10, 2005·Seminars in Cell & Developmental Biology·Dan LuoThomas A Rando
Jun 3, 2006·Journal of Cellular Physiology·Magali KitzmannGilles Carnac
Jan 18, 2007·Journal of Cellular Biochemistry·Andrei V KrivtsovAlexander V Belyavsky
Jan 24, 2007·Neuromuscular Disorders : NMD·L HartleyF Muntoni
May 15, 2007·Experimental Cell Research·Emiko Suzuki, Manabu Nakayama
Dec 7, 2007·The Journal of Cell Biology·Chet E HoltermanMichael A Rudnicki
Feb 2, 2008·BMC Developmental Biology·Sarah J BrayAnne C Ferguson-Smith
Apr 23, 2008·Current Protocols in Human Genetics·Matthew L SpringerHelen M Blau
May 11, 2010·Experimental Cell Research·Matthew F Buas, Tom Kadesch
Dec 3, 2010·PloS One·Jolena N WaddellShihuan Kuang
Jan 7, 2011·American Journal of Physiology. Cell Physiology·Kenneth W DunnJohn H McDonald
Aug 21, 2013·FEBS Letters·Satomi MitsuhashiPeter B Kang
Aug 29, 2013·International Journal of Cell Biology·Maria Francesca Mossuto
Jan 1, 2011·Pharmaceutics·Keren I Hulkower, Renee L Herber
Jan 15, 2014·PLoS Genetics·Sujin Bao
May 2, 2014·Human Molecular Genetics·Aiping LuJohnny Huard
May 3, 2014·The Journal of Clinical Investigation·Matthew S AlexanderLouis M Kunkel
Aug 12, 2014·The American Journal of Pathology·Isabelle DraperPeter B Kang
Nov 12, 2014·Molecular and Cellular Biology·Audrey Der VartanianAgnès Germot
Nov 17, 2015·Nature Medicine·Nicolas A DumontMichael A Rudnicki

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Citations

Aug 3, 2018·Human Gene Therapy·Silveli Suzuki-HatanoChristina A Pacak
Feb 26, 2019·FEBS Letters·Isabelle DraperPeter B Kang
Jul 4, 2019·Human Molecular Genetics·Madhurima SahaPeter B Kang
Apr 17, 2021·American Journal of Human Genetics·Sandra CoppensPeter B Kang
Dec 9, 2021·Médecine sciences : M/S·Rocio Nur Villar-QuilesStojkovic Tanya

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