Phosphorylation of ryanodine receptors

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Cristina I Danila1, Susan L Hamilton

  • 1Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA.

Biological Research
|February 16, 2005
PubMed

Insights

Phosphorylation of muscle ryanodine receptors (RyRs) is controversial. Key sites like Ser-2809 (cardiac RyR2) and Ser-2843 (skeletal RyR1) may cause leaky channels, but enzyme identities and FKBP binding remain debated.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Physiology

Background:

  • Muscle ryanodine receptors (RyRs) are large protein complexes involved in calcium release.
  • These receptors possess cytoplasmic phosphorylation sites, but their functional significance and regulatory enzymes are debated.
  • Controversies exist regarding the link between RyR hyperphosphorylation, FKBP binding, and channel "leakiness".

Purpose of the Study:

  • To review major findings and controversies surrounding RyR phosphorylation.
  • To discuss the functional consequences of RyR phosphorylation, particularly at Ser-2809 (RyR2) and Ser-2843 (RyR1).
  • To explore the roles of kinases like PKA and CaMKII in RyR phosphorylation and calcium homeostasis.

Main Methods:

  • Literature review of studies on RyR phosphorylation.
  • Analysis of research investigating kinase and phosphatase interactions with RyRs.
  • Examination of evidence linking phosphorylation to FKBP binding and channel function.

Main Results:

  • Hyperphosphorylation of RyR2 (Ser-2809) and RyR1 (Ser-2843) is proposed to cause FKBP dissociation and channel "leak."
  • Conflicting data exists regarding the relationship between RyR phosphorylation and FKBP binding.
  • The specific kinases (PKA vs. CaMKII) responsible for phosphorylating these sites remain under debate.
  • Phosphorylation of other targets, like phospholamban (PLB) by PKA, impacts SERCA activity and calcium handling.

Conclusions:

  • The functional consequences of RyR phosphorylation are complex and debated.
  • Further research is needed to clarify the roles of specific kinases and phosphorylation sites in RyR function and calcium regulation.
  • Understanding RyR phosphorylation is crucial for comprehending muscle excitation-contraction coupling and related disorders.

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