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11:31
Crystal Structure of the N-terminal Domain of Ryanodine Receptor from Plutella xylostella
Published on: November 30, 2018
Modulation of ryanodine receptor Ca2+ channels (Review)
1Department of Physiology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan. teozawa@mail.tains.tohoku.ac.jp.
Molecular Medicine Reports
|April 8, 2011
Summary
Ryanodine receptors (RyRs) are crucial for muscle contraction. Associated proteins and phosphorylation modulate RyR activity, impacting calcium release from the sarcoplasmic reticulum.
Area of Science:
- Muscle Physiology
- Molecular Biology
- Calcium Signaling
Background:
- Ryanodine receptors (RyRs) are critical for excitation-contraction coupling in muscle cells, mediating calcium (Ca2+) release from the sarcoplasmic reticulum (SR).
- RyR activation mechanisms differ between skeletal (depolarization) and cardiac muscle (Ca2+ influx), with various activators (caffeine, cyclic ADP-ribose) and inhibitors (Mg2+, ruthenium red) identified.
Purpose of the Study:
- To review the diverse mechanisms by which associated proteins and phosphorylation modulate ryanodine receptor (RyR) activity.
- To elucidate the functional roles of calmodulin (CaM), calsequestrin (CSQ), and FK506-binding proteins (FKBPs) in RyR regulation.
Main Methods:
- Literature review focusing on the molecular interactions and regulatory pathways of RyR channels.
- Analysis of studies investigating the effects of protein binding and post-translational modifications (phosphorylation) on RyR function.
Main Results:
- Associated proteins like CaM, CSQ, and FKBPs significantly influence RyR channel gating and Ca2+ release.
- Ca2+-free CaM activates RyRs, while Ca2+-bound CaM inhibits them; CSQ facilitates Ca2+ release upon RyR stimulation.
- FKBP12/12.6 dissociation from RyRs leads to channel activation, and PKA-mediated phosphorylation can trigger this dissociation.
Conclusions:
- RyR function is intricately regulated by a complex interplay of associated proteins and phosphorylation events.
- Understanding these modulation mechanisms is key to comprehending muscle excitation-contraction coupling and potential therapeutic targets.
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