Selenoprotein N is required for ryanodine receptor calcium release channel activity in human and zebrafish muscle.

摘要: Mutations affecting the seemingly unrelated gene products, SepN1, a selenoprotein of unknown function, and RyR1, major component ryanodine receptor intracellular calcium release channel, result in an overlapping spectrum congenital myopathies. To identify immediate developmental molecular roles SepN RyR vivo, loss-of-function effects were analyzed zebrafish embryo. These studies demonstrate two proteins are required for same cellular differentiation events needed normal fluxes is physically associated with RyRs functions as modifier channel. In absence SepN, receptors from embryos or human diseased muscle have altered biochemical properties lost their sensitivity to redox conditions, which likely accounts why mutations either factor lead similar diseases.