title: Selenoprotein N is required for ryanodine receptor calcium release channel activity in human and zebrafish muscle.
abstract: Mutations affecting the seemingly unrelated gene products, SepN1, a selenoprotein of unknown function, and RyR1, the major component of the ryanodine receptor intracellular calcium release channel, result in an overlapping spectrum of congenital myopathies. To identify the immediate developmental and molecular roles of SepN and RyR in vivo, loss-of-function effects were analyzed in the zebrafish embryo. These studies demonstrate the two proteins are required for the same cellular differentiation events and are needed for normal calcium fluxes in the embryo. SepN is physically associated with RyRs and functions as a modifier of the RyR channel. In the absence of SepN, ryanodine receptors from zebrafish embryos or human diseased muscle have altered biochemical properties and have lost their normal sensitivity to redox conditions, which likely accounts for why mutations affecting either factor lead to similar diseases.
authors: Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA.
authors: Michael J
authors: MJ
authors: Jurynec
authors: Ruohong
authors: R
authors: Xia
authors: John J
authors: JJ
authors: Mackrill
authors: Derrick
authors: D
authors: Gunther
authors: Thomas
authors: T
authors: Crawford
authors: Kevin M
authors: KM
authors: Flanigan
authors: Jonathan J
authors: JJ
authors: Abramson
authors: Michael T
authors: MT
authors: Howard
authors: David Jonah
authors: DJ
authors: Grunwald
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D002648:Child; D004198:Disease Susceptibility; D004625:Embryo, Nonmammalian; D005260:Female; D006801:Humans; D008969:Molecular Sequence Data; D024510:Muscle Development; D018657:Muscle Fibers, Slow-Twitch; D009124:Muscle Proteins / Q000502:physiology*; D009132:Muscles / Q000166:cytology / Q000378:metabolism*; D009135:Muscular Diseases; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism* / Q000502:physiology; D051140:Selenoproteins / Q000502:physiology*; D015027:Zebrafish
chemical_list: D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; C435489:SELENON protein, human; D051140:Selenoproteins; D002118:Calcium