Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Sarcolipin

  • Sushant Singh
  • Sanjaya K. Sahoo
  • Muthu Periasamy
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101787

Synonyms

 SLN

Historical Background

Sarcolipin (SLN) was first identified by David MacLennan in 1974 as a “proteolipid” in purified rabbit skeletal muscle sarcoplasmic reticulum (SR) preparations (MacLennan 1974). In 1992, Wawrzynow et al. determined its sequence, confirmed its molecular weight as 3,733 Da, and named it sarcolipin (SLN) with reference to its nature and origin (Wawrzynow et al. 1992). SLN protein sequence is highly conserved from fish to man. For nearly three decades, the exact function of SLN remained unknown. Early studies suggested that it is very similar to phospholamban (PLB), an important regulator of the SERCA pump in cardiac muscle (Fig. 1). Using reconstituted synthetic SLN and SERCA, Lee et al. first proposed the idea that SLN binding to SERCA could promote uncoupling of SERCA ATP hydrolysis from Ca 2+ transport (Mall et al. 2006). More recent studies from our laboratory have shown that SLN binding to SERCA causes uncoupling of SR Ca 2+transport from ATP...
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References

  1. Asahi M, Kurzydlowski K, Tada M, MacLennan DH. Sarcolipin inhibits polymerization of phospholamban to induce superinhibition of sarco (endo) plasmic reticulum Ca2+-ATPases (SERCAs). J Biol Chem. 2002;277(30):26725–8.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Asahi M, Sugita Y, Kurzydlowski K, De Leon S, Tada M, Toyoshima C, et al. Sarcolipin regulates sarco (endo) plasmic reticulum Ca2+-ATPase (SERCA) by binding to transmembrane helices alone or in association with phospholamban. Proc Natl Acad Sci USA. 2003;100(9):5040–5.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Babu GJ, Bhupathy P, Carnes CA, Billman GE, Periasamy M. Differential expression of sarcolipin protein during muscle development and cardiac pathophysiology. J Mol Cell Cardiol. 2007a;43(2):215–22.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Babu GJ, Bhupathy P, Timofeyev V, Petrashevskaya NN, Reiser PJ, Chiamvimonvat N, et al. Ablation of sarcolipin enhances sarcoplasmic reticulum calcium transport and atrial contractility. Proc Natl Acad Sci USA. 2007b;104(45):17867–72.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Bal NC, Maurya SK, Sopariwala DH, Sahoo SK, Gupta SC, Shaikh SA, et al. Sarcolipin is a newly identified regulator of muscle-based thermogenesis in mammals. Nat Med. 2012;18(10):1575–9.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Gramolini AO, Kislinger T, Asahi M, Li W, Emili A, MacLennan DH. Sarcolipin retention in the endoplasmic reticulum depends on its C-terminal RSYQY sequence and its interaction with sarco (endo) plasmic Ca2+-ATPases. Proc Natl Acad Sci USA. 2004;101(48):16807–12.PubMedPubMedCentralCrossRefGoogle Scholar
  7. MacLennan DH. Isolation of proteins of the sarcoplasmic reticulum. Methods Enzymol. 1974;32:291.PubMedPubMedCentralCrossRefGoogle Scholar
  8. MacLennan DH, Kranias EG. Phospholamban: a crucial regulator of cardiac contractility. Nat Rev Mol Cell Biol. 2003;4(7):566–77.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Mall S, Broadbridge R, Harrison SL, Gore MG, Lee AG, East JM. The presence of sarcolipin results in increased heat production by Ca2+-ATPase. J Biol Chem. 2006;281(48):36597–602.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Maurya SK, Bal NC, Sopariwala DH, Pant M, Rowland LA, Shaikh SA, et al. Sarcolipin is a key determinant of the basal metabolic rate, and its overexpression enhances energy expenditure and resistance against diet-induced obesity. J Biol Chem. 2015;290(17):10840–9.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Sahoo SK, Shaikh SA, Sopariwala DH, Bal NC, Periasamy M. Sarcolipin protein interaction with sarco (endo) plasmic reticulum Ca2+ ATPase (SERCA) is distinct from phospholamban protein, and only sarcolipin can promote uncoupling of the SERCA pump. J Biol Chem. 2013;288(10):6881–9.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Sahoo SK, Shaikh SA, Sopariwala DH, Bal NC, Bruhn DS, Kopec W, et al. The N terminus of sarcolipin plays an important role in uncoupling sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) ATP hydrolysis from Ca2+ transport. J Biol Chem. 2015;290(22):14057–67.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Shaikh SA, Sahoo SK, Periasamy M. Phospholamban and sarcolipin: are they functionally redundant or distinct regulators of the sarco (endo) plasmic reticulum calcium ATPase? J Mol Cell Cardiol. 2016;91:81–91.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Toyoshima C, Iwasawa S, Ogawa H, Hirata A, Tsueda J, Inesi G. Crystal structures of the calcium pump and sarcolipin in the Mg2+-bound E1 state. Nature. 2013;495(7440):260–4.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Wawrzynow A, Theibert JL, Murphy C, Jona I, Martonosi A, Collins JH. Sarcolipin, the “proteolipid” of skeletal muscle sarcoplasmic reticulum, is a unique, amphipathic, 31-residue peptide. Arch Biochem Biophys. 1992;298(2):620–3.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Winther A-ML, Bublitz M, Karlsen JL, Møller JV, Hansen JB, Nissen P, et al. The sarcolipin-bound calcium pump stabilizes calcium sites exposed to the cytoplasm. Nature. 2013;495(7440):265–9.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Sushant Singh
    • 1
  • Sanjaya K. Sahoo
    • 1
  • Muthu Periasamy
    • 1
  1. 1.Center for Metabolic Origins of Disease, Cardiovascular Metabolism ProgramSanford Burnham Prebys Medical Discovery InstituteOrlandoUSA