Key result
Wild-type MEGF10 overexpression enhances myoblast proliferation vs Y1030F mutation, confirming its regulatory signaling role.
Why the study?
Recessive mutations in MEGF10 cause congenital myopathy, but the impact of cysteine mutations on MEGF10 tyrosine phosphorylation and myoblast proliferation was unclear.
MEGF10-mediated signaling via tyrosine phosphorylation regulates myoblast proliferation, and defects in this pathway may contribute to the disease mechanism of MEGF10 myopathy.
Implicates MEGF10 signaling in myopathy mechanisms; hypothesis-generating and requires validation before clinical consideration.
Recessive mutations in MEGF10 are known to cause a congenital myopathy in humans. Two mutations in the extracellular EGF-like domains of MEGF10, C326R and C774R, were associated with decreased tyrosine phosphorylation of MEGF10 in vitro. Y1030 was identified to be the major tyrosine phosphorylation site in MEGF10 and is phosphorylated at least in part by c-Src. Overexpression of wild-type MEGF10 enhanced C2C12 myoblast proliferation, while overexpression of Y1030F mutated MEGF10 did not. We conclude that MEGF10-mediated signaling via tyrosine phosphorylation helps to regulate myoblast proliferation. Defects in this signaling pathway may contribute to the disease mechanism of MEGF10 myopathy.
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Mitsuhashi et al. (2013) studied MEGF10 myopathy. MEGF10 mutations (C326R, C774R, Y1030F) vs. Wild-type MEGF10 was evaluated on Tyrosine phosphorylation and myoblast proliferation. Overexpression of wild-type MEGF10 enhanced C2C12 myoblast proliferation, whereas Y1030F mutated MEGF10 did not, indicating that MEGF10-mediated signaling regulates myoblast proliferation.
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