The regulation of sarco(endo)plasmic reticulum calcium-ATPases (SERCA).
The sarco(endo)plasmic reticulum calcium ATPase (SERCA) is responsible for transporting calcium (Ca(2+)) from the cytosol into the lumen of the sarcoplasmic reticulum (SR) following muscular contraction. The Ca(2+) sequestering activity of SERCA facilitates muscular relaxation in both cardiac and skeletal muscle. There are more than 10 distinct isoforms of SERCA expressed in different tissues. SERCA2a is the primary isoform expressed in cardiac tissue, whereas SERCA1a is the predominant isoform expressed in fast-twitch skeletal muscle. The Ca(2+) sequestering activity of SERCA is regulated at the level of protein content and is further modified by the endogenous proteins phospholamban (PLN) and sarcolipin (SLN). Additionally, several novel mechanisms, including post-translational modifications and microRNAs (miRNAs) are emerging as integral regulators of Ca(2+) transport activity. These regulatory mechanisms are clinically relevant, as dysregulated SERCA function has been implicated in the pathology of several disease states, including heart failure. Currently, several clinical trials are underway that utilize novel therapeutic approaches to restore SERCA2a activity in humans. The purpose of this review is to examine the regulatory mechanisms of the SERCA pump, with a particular emphasis on the influence of exercise in preventing the pathological conditions associated with impaired SERCA function.
a Health, Leisure & Human Performance Research Institute, Faculty of Kinesiology & Recreation Management, University of Manitoba.|b Institute of Cardiovascular Sciences, St. Boniface Hospital Research Centre.
Andrew N
AN
Stammers
b Institute of Cardiovascular Sciences, St. Boniface Hospital Research Centre.|c Department of Physiology, Faculty of Health Sciences, University of Manitoba.
Shanel E
SE
Susser
a Health, Leisure & Human Performance Research Institute, Faculty of Kinesiology & Recreation Management, University of Manitoba.|b Institute of Cardiovascular Sciences, St. Boniface Hospital Research Centre.
Naomi C
NC
Hamm
a Health, Leisure & Human Performance Research Institute, Faculty of Kinesiology & Recreation Management, University of Manitoba.|b Institute of Cardiovascular Sciences, St. Boniface Hospital Research Centre.
Michael W
MW
Hlynsky
a Health, Leisure & Human Performance Research Institute, Faculty of Kinesiology & Recreation Management, University of Manitoba.|b Institute of Cardiovascular Sciences, St. Boniface Hospital Research Centre.
Dustin E
DE
Kimber
a Health, Leisure & Human Performance Research Institute, Faculty of Kinesiology & Recreation Management, University of Manitoba.|b Institute of Cardiovascular Sciences, St. Boniface Hospital Research Centre.
D Scott
DS
Kehler
a Health, Leisure & Human Performance Research Institute, Faculty of Kinesiology & Recreation Management, University of Manitoba.|b Institute of Cardiovascular Sciences, St. Boniface Hospital Research Centre.|c Department of Physiology, Faculty of Health Sciences, University of Manitoba.
Todd A
TA
Duhamel
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000201:enzymology; D005081:Exercise Therapy; D006333:Heart Failure / Q000235:genetics / Q000517:prevention & control / Q000628:therapy; D006801:Humans; D009124:Muscle Proteins / Q000378:metabolism; D009126:Muscle Relaxation / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism; D009130:Muscle, Smooth / Q000378:metabolism; D009200:Myocardial Contraction / Q000502:physiology; D011510:Proteolipids / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics; D012519:Sarcoplasmic Reticulum / Q000201:enzymology*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism*; D000099211:Phospholamban
D002118:Calcium; D002135:Calcium-Binding Proteins; D009124:Muscle Proteins; D011510:Proteolipids; D012333:RNA, Messenger; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000099211:Phospholamban; C077258:sarcolipin
calcium (Ca2+); cardiac muscle; exercice; exercise; heart failure; insuffisance cardiaque; modifications post-traductionnelles; muscle cardiaque; muscle squelettique; phospholamban (PLN); post-translational modifications; sarcolipin (SLN); sarcolipine (SLN); skeletal muscle