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

Michael J. Jurynec, Ruohong Xia, John J. Mackrill, Derrick Gunther, Thomas Crawford, Kevin M. Flanigan, Jonathan J. Abramson, Michael T. Howard, David Jonah Grunwald

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)12485-12490
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number34
DOIs
StatePublished - Aug 26 2008

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Keywords

  • Congenital myopathy
  • Disease model
  • Intracellular calcium release

ASJC Scopus subject areas

  • General

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