Calsequestrin interacts directly with the cardiac ryanodine receptor luminal domain.
Cardiac muscle contraction requires sarcoplasmic reticulum (SR) Ca2+release mediated by the quaternary complex comprising the ryanodine receptor 2 (RyR2), calsequestrin 2 (CSQ2), junctin (encoded by ASPH) and triadin. Here, we demonstrate that a direct interaction exists between RyR2 and CSQ2. Topologically, CSQ2 binding occurs at the first luminal loop of RyR2. Co-expression of RyR2 and CSQ2 in a human cell line devoid of the other quaternary complex proteins results in altered Ca2+-release dynamics compared to cells expressing RyR2 only. These findings provide a new perspective for understanding the SR luminal Ca2+sensor and its involvement in cardiac physiology and disease.
Sir Geraint Evans Wales Heart Research Institute, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK.|Medical Biochemistry Department, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.
Ahmed
A
Handhle
Sir Geraint Evans Wales Heart Research Institute, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK.
Chloe E
CE
Ormonde
Sir Geraint Evans Wales Heart Research Institute, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK.
N Lowri
NL
Thomas
Sir Geraint Evans Wales Heart Research Institute, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK.
Catherine
C
Bralesford
Sir Geraint Evans Wales Heart Research Institute, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK.
Alan J
AJ
Williams
Sir Geraint Evans Wales Heart Research Institute, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK.
F Anthony
FA
Lai
Sir Geraint Evans Wales Heart Research Institute, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK zissimopouloss@cardiff.ac.uk.
Spyros
0000-0001-5196-9450
S
Zissimopoulos
D002118:Calcium / Q000378:metabolism; D002155:Calsequestrin / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D011485:Protein Binding; D000072417:Protein Domains; D025941:Protein Interaction Mapping; D017433:Protein Structure, Secondary; D019837:Ryanodine Receptor Calcium Release Channel / Q000737:chemistry / Q000378:metabolism*
D002155:Calsequestrin; D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium
Ca2+ intracellular release; Calsequestrin; Excitation-contraction coupling; Luminal Ca2+ sensor; Protein–protein interaction; Ryanodine receptor; Sarcoplasmic reticulum