PUBLICATION

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

Authors
Jurynec, M.J., Xia, R., Mackrill, J.J., Gunther, D., Crawford, T., Flanigan, K.M., Abramson, J.J., Howard, M.T., and Grunwald, D.J.
ID
ZDB-PUB-080826-31
Date
2008
Source
Proceedings of the National Academy of Sciences of the United States of America   105(34): 12485-12490 (Journal)
Registered Authors
Grunwald, David, Jurynec, Michael
Keywords
congenital myopathy, disease model, intracellular calcium release
MeSH Terms
  • Muscle Proteins/physiology*
  • Molecular Sequence Data
  • Humans
  • Female
  • Disease Susceptibility
  • Muscle Fibers, Slow-Twitch
  • Child
  • Selenoproteins/physiology*
  • Muscle Development*
  • Muscles/cytology
  • Muscles/metabolism*
  • Zebrafish
  • Calcium/metabolism
  • Embryo, Nonmammalian
  • Muscular Diseases
  • Ryanodine Receptor Calcium Release Channel/metabolism*
  • Ryanodine Receptor Calcium Release Channel/physiology
  • Cell Differentiation
  • Animals
(all 19)
PubMed
18713863 Full text @ Proc. Natl. Acad. Sci. USA
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.
Genes / Markers
Figures
Figure Gallery (10 images)
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Expression
Phenotype
Mutations / Transgenics
No data available
Human Disease / Model
No data available
Sequence Targeting Reagents
Target Reagent Reagent Type
ryr1aMO1-ryr1aMRPHLNO
ryr1aMO2-ryr1aMRPHLNO
ryr3MO1-ryr3MRPHLNO
selenonMO5-selenonMRPHLNO
selenonMO6-selenonMRPHLNO
1 - 5 of 5
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Fish
Antibodies
Orthology
No data available
Engineered Foreign Genes
No data available
Mapping
No data available