title: Phospholamban and sarcolipin: Are they functionally redundant or distinct regulators of the Sarco(Endo)Plasmic Reticulum Calcium ATPase?
abstract: In muscle, the Sarco(Endo)plasmic Reticulum Calcium ATPase (SERCA) activity is regulated by two distinct proteins, PLB and SLN, which are highly conserved throughout vertebrate evolution. PLB is predominantly expressed in the cardiac muscle, while SLN is abundant in skeletal muscle. SLN is also found in the cardiac atria and to a lesser extent in the ventricle. PLB regulation of SERCA is central to cardiac function, both at rest and during extreme physiological demand. Compared to PLB, the physiological relevance of SLN remained a mystery until recently and some even thought it was redundant in function. Studies on SLN suggest that it is an uncoupler of the SERCA pump activity and can increase ATP hydrolysis resulting in heat production. Using genetically engineered mouse models for SLN and PLB, we showed that SLN, not PLB, is required for muscle-based thermogenesis. However, the mechanism of how SLN binding to SERCA results in uncoupling SERCA Ca(2+) transport from its ATPase activity remains unclear. In this review, we discuss recent advances in understanding how PLB and SLN differ in their interaction with SERCA. We will also explore whether structural differences in the cytosolic domain of PLB and SLN are the basis for their unique function and physiological roles in cardiac and skeletal muscle.
authors.affiliation: Center for Metabolic Origins of Disease, Cardiovascular Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute, Lake Nona, FL. 6400 Sanger Road, Orlando, FL 32827, United States.
authors.forename: Sana A
authors.initials: SA
authors.lastname: Shaikh
authors.affiliation: Center for Metabolic Origins of Disease, Cardiovascular Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute, Lake Nona, FL. 6400 Sanger Road, Orlando, FL 32827, United States.
authors.forename: Sanjaya K
authors.initials: SK
authors.lastname: Sahoo
authors.affiliation: Center for Metabolic Origins of Disease, Cardiovascular Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute, Lake Nona, FL. 6400 Sanger Road, Orlando, FL 32827, United States. Electronic address: mperiasamy@sbpdiscovery.org.
authors.forename: Muthu
authors.initials: M
authors.lastname: Periasamy
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D017136:Ion Transport; D051379:Mice; D009124:Muscle Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011510:Proteolipids / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D022722:Thermogenesis / Q000502:physiology; D000099211:Phospholamban
chemical_list: D000255:Adenosine Triphosphate; D002118:Calcium; D002135:Calcium-Binding Proteins; D009124:Muscle Proteins; D011510:Proteolipids; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000099211:Phospholamban; C077258:sarcolipin
keywords: Ca(2+) transport; Phospholamban; SERCA; Sarcolipin