Control of muscle ryanodine receptor calcium release channels by proteins in the sarcoplasmic reticulum lumen.
1. Many biological processes that are governed by intracellular calcium signals rely on intracellular stores, which provide a reliable, controlled release of calcium into the cytoplasm. Calcium release through the ryanodine receptor (RyR), the main ion channel in the sarcoplasmic reticulum (the calcium store in muscle) is the key determinant of muscle force. 2. Calsequestrin, the main calcium buffer in the sarcoplasmic reticulum, provides a pool of calcium for release through the RyR and acts as a luminal calcium sensor for the channel via its interactions with triadin and junctin. Until recently, how calsequestrin communicated the store Ca(2+) load to the RyR remained unknown. 3. Calsequestrin 1 (skeletal calsequestrin) has been shown to both inhibit and activate the skeletal RyR1, dependent on whether it's bound to the RyR1 directly or indirectly via anchoring proteins. 4. The phosphorylation status of calsequestrin 1 is deemed important: it influences the Ca(2+) binding capacity of calsequestrin, the way in which calsequestrin 1 regulates the RyR1 and how calsequestrin 1 interacts with the key anchoring protein junctin. 5. In skeletal muscle, junctin plays a more critical role than triadin in the mechanism that controls Ca(2+) release from the sarcoplasmic reticulum. 6. The close relationship between altered expression and dysfunction of calsequestrin in several skeletal and cardiac disorders highlights the critical role that calsequestrin plays in maintaining Ca(2+) homeostasis and regulation of muscle contraction.
Beard
Nicole A
NA
John Curtin School of Medical Research, Australian National University, ACT, Australia. nicole.beard@anu.edu.au
Wei
Lan
L
Dulhunty
Angela F
AF
D000818:Animals; D020013:Calcium Signaling; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002155:Calsequestrin / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009119:Muscle Contraction; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D009135:Muscular Diseases / Q000378:metabolism; D010766:Phosphorylation; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*
D002135:Calcium-Binding Proteins; D002155:Calsequestrin; D002352:Carrier Proteins; D008565:Membrane Proteins; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; C070048:triadin; D006899:Mixed Function Oxygenases; C419389:ASPH protein, human