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J Mol Cell Cardiol. 2016 Feb;91:81-91. doi: 10.1016/j.yjmcc.2015.12.030. Epub 2015 Dec 29.

Phospholamban and sarcolipin: Are they functionally redundant or distinct regulators of the Sarco(Endo)Plasmic Reticulum Calcium ATPase?

Author information

1
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.
2
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.

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.

KEYWORDS:

Ca(2+) transport; Phospholamban; SERCA; Sarcolipin

PMID:
26743715
PMCID:
PMC4843517
DOI:
10.1016/j.yjmcc.2015.12.030
[Indexed for MEDLINE]
Free PMC Article

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