TY - JOUR
T1 - Ryanodine receptor Ca 2+ release channel post-translational modification
T2 - Central player in cardiac and skeletal muscle disease
AU - Denniss, Amanda
AU - Dulhunty, Angela F.
AU - Beard, Nicole A.
PY - 2018/8/1
Y1 - 2018/8/1
N2 -
Calcium release from internal stores is a quintessential event in excitation-contraction coupling in cardiac and skeletal muscle. The ryanodine receptor Ca
2+
release channel is embedded in the internal sarcoplasmic reticulum Ca
2+
store, which releases Ca
2+
into the cytoplasm, enabling contraction. Ryanodine receptors form the hub of a macromolecular complex extending from the extracellular space to the sarcoplasmic reticulum lumen. Ryanodine receptor activity is influenced by the integrated effects of associated co-proteins, ions, and post-translational phosphor and redox modifications. In healthy muscle, ryanodine receptors are phosphorylated and redox modified to basal levels, to support cellular function. A pathological increase in the degree of both post-translational modifications disturbs intracellular Ca
2+
signalling, and is implicated in various cardiac and skeletal disorders. This review summarises our current understanding of the mechanisms linking ryanodine receptor post-translational modification to heart failure and skeletal myopathy and highlights the challenges and controversies within the field.
AB -
Calcium release from internal stores is a quintessential event in excitation-contraction coupling in cardiac and skeletal muscle. The ryanodine receptor Ca
2+
release channel is embedded in the internal sarcoplasmic reticulum Ca
2+
store, which releases Ca
2+
into the cytoplasm, enabling contraction. Ryanodine receptors form the hub of a macromolecular complex extending from the extracellular space to the sarcoplasmic reticulum lumen. Ryanodine receptor activity is influenced by the integrated effects of associated co-proteins, ions, and post-translational phosphor and redox modifications. In healthy muscle, ryanodine receptors are phosphorylated and redox modified to basal levels, to support cellular function. A pathological increase in the degree of both post-translational modifications disturbs intracellular Ca
2+
signalling, and is implicated in various cardiac and skeletal disorders. This review summarises our current understanding of the mechanisms linking ryanodine receptor post-translational modification to heart failure and skeletal myopathy and highlights the challenges and controversies within the field.
KW - Myopathy
KW - Phosphorylation
KW - Reactive oxygen species
KW - Ryanodine receptor
KW - Reactive Oxygen Species/metabolism
KW - Ryanodine Receptor Calcium Release Channel/genetics
KW - Heart Failure/genetics
KW - Humans
KW - Sarcoplasmic Reticulum/metabolism
KW - Muscle, Skeletal/metabolism
KW - Myotonia Congenita/genetics
KW - Calcium/metabolism
KW - Animals
KW - Myocardium/metabolism
KW - Excitation Contraction Coupling/physiology
KW - Protein Processing, Post-Translational
KW - Muscle Contraction/physiology
KW - Calcium Signaling
UR - http://www.scopus.com/inward/record.url?scp=85047653876&partnerID=8YFLogxK
UR - http://www.mendeley.com/research/ryanodine-receptor-ca-2-release-channel-posttranslational-modification-central-player-cardiac-skelet
U2 - 10.1016/j.biocel.2018.05.004
DO - 10.1016/j.biocel.2018.05.004
M3 - Article
C2 - 29775742
AN - SCOPUS:85047653876
SN - 1357-2725
VL - 101
SP - 49
EP - 53
JO - International Journal of Biochemistry and Cell Biology
JF - International Journal of Biochemistry and Cell Biology
ER -