Sarcolipin Explained

Sarcolipin is a micropeptide protein that in humans is encoded by the SLN gene.^{[1] [2]}

Function

Sarcoplasmic reticulum Ca²⁺-ATPases are transmembrane proteins that catalyze the ATP-dependent transport of Ca²⁺ from the cytosol into the lumen of the sarcoplasmic reticulum in muscle cells. The SLN gene encodes a small transmembrane proteolipid that regulates several sarcoplasmic reticulum Ca²⁺-ATPases by reducing the accumulation of Ca²⁺ in the sarcoplasmic reticulum without affecting the rate of ATP hydrolysis.^[2]

Ablation of sarcolipin increases atrial Ca²⁺ transient amplitudes and enhanced atrial contractility. Furthermore, atria from sarcolipin-null mice have blunted response to isoproterenol stimulation, implicating sarcolipin as a mediator of beta-adrenergic responses in atria.^[3]

Sarcolipin is an important mediator of muscle based non shivering thermogenesis (NST). It causes the sarcoplasmic reticulum Ca²⁺-ATPases to stop pumping Ca²⁺ ions but continue futilely hydrolysing ATP, thus releasing the energy as heat.^{[4] [5]} Sarcolipin mediated heat production is very important for many organisms to maintain a warm body. In mammals thermogenesis by skeletal muscles is complemented by thermogenesis in the brown adipose tissue and beige adipose tissue. ^[6] Sarcolipin mediated heat production in contractile muscles helps endothermic fish like the opah heat its body. Some fishes like the billfishes have a specialised brain heater tissue that is derived from muscles that cannot contract but specialise in producing heat using sarcolipin.

Interactions

SLN (gene) has been shown to interact with PLN^{[7] [8]} and ATP2A1.^{[7] [8]}

References

Further reading

• Lanfranchi G, Muraro T, Caldara F, Pacchioni B, Pallavicini A, Pandolfo D, Toppo S, Trevisan S, Scarso S, Valle G . 6 . Identification of 4370 expressed sequence tags from a 3'-end-specific cDNA library of human skeletal muscle by DNA sequencing and filter hybridization . Genome Research . 6 . 1 . 35–42 . January 1996 . 8681137 . 10.1101/gr.6.1.35 . free .
• Odermatt A, Becker S, Khanna VK, Kurzydlowski K, Leisner E, Pette D, MacLennan DH . Sarcolipin regulates the activity of SERCA1, the fast-twitch skeletal muscle sarcoplasmic reticulum Ca2+-ATPase . The Journal of Biological Chemistry . 273 . 20 . 12360–9 . May 1998 . 9575189 . 10.1074/jbc.273.20.12360 . free .
• Smith WS, Broadbridge R, East JM, Lee AG . Sarcolipin uncouples hydrolysis of ATP from accumulation of Ca2+ by the Ca2+-ATPase of skeletal-muscle sarcoplasmic reticulum . The Biochemical Journal . 361 . Pt 2 . 277–86 . January 2002 . 11772399 . 1222307 . 10.1042/0264-6021:3610277 .
• Mascioni A, Karim C, Barany G, Thomas DD, Veglia G . Structure and orientation of sarcolipin in lipid environments . Biochemistry . 41 . 2 . 475–82 . January 2002 . 11781085 . 10.1021/bi011243m .
• Asahi M, Kurzydlowski K, Tada M, MacLennan DH . Sarcolipin inhibits polymerization of phospholamban to induce superinhibition of sarco(endo)plasmic reticulum Ca2+-ATPases (SERCAs) . The Journal of Biological Chemistry . 277 . 30 . 26725–8 . July 2002 . 12032137 . 10.1074/jbc.C200269200 . free .
• Minamisawa S, Wang Y, Chen J, Ishikawa Y, Chien KR, Matsuoka R . Atrial chamber-specific expression of sarcolipin is regulated during development and hypertrophic remodeling . The Journal of Biological Chemistry . 278 . 11 . 9570–5 . March 2003 . 12645548 . 10.1074/jbc.M213132200 . free .
• Asahi M, Sugita Y, Kurzydlowski K, De Leon S, Tada M, Toyoshima C, MacLennan DH . Sarcolipin regulates sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) by binding to transmembrane helices alone or in association with phospholamban . Proceedings of the National Academy of Sciences of the United States of America . 100 . 9 . 5040–5 . April 2003 . 12692302 . 154294 . 10.1073/pnas.0330962100 . 2003PNAS..100.5040A . free .
• Suzuki Y, Yamashita R, Shirota M, Sakakibara Y, Chiba J, Mizushima-Sugano J, Nakai K, Sugano S . 6 . Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions . Genome Research . 14 . 9 . 1711–8 . September 2004 . 15342556 . 515316 . 10.1101/gr.2435604 .
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M . 6 . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . October 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
• Vittorini S, Storti S, Parri MS, Cerillo AG, Clerico A . SERCA2a, phospholamban, sarcolipin, and ryanodine receptors gene expression in children with congenital heart defects . Molecular Medicine . 13 . 1–2 . 105–11 . 2007 . 17515962 . 1869624 . 10.2119/2006-00054.Vittorini .

Notes and References

1. Odermatt A, Taschner PE, Scherer SW, Beatty B, Khanna VK, Cornblath DR, Chaudhry V, Yee WC, Schrank B, Karpati G, Breuning MH, Knoers N, MacLennan DH . 6 . Characterization of the gene encoding human sarcolipin (SLN), a proteolipid associated with SERCA1: absence of structural mutations in five patients with Brody disease . Genomics . 45 . 3 . 541–53 . November 1997 . 9367679 . 10.1006/geno.1997.4967 . 2066/25426 . 41989102 . free .
2. Web site: Entrez Gene: SLN sarcolipin.
3. Babu GJ, Bhupathy P, Timofeyev V, Petrashevskaya NN, Reiser PJ, Chiamvimonvat N, Periasamy M . Ablation of sarcolipin enhances sarcoplasmic reticulum calcium transport and atrial contractility . Proceedings of the National Academy of Sciences of the United States of America . 104 . 45 . 17867–72 . November 2007 . 17971438 . 2077025 . 10.1073/pnas.0707722104 . 2007PNAS..10417867B . free .
4. Bal NC, Periasamy M . Uncoupling of sarcoendoplasmic reticulum calcium ATPase pump activity by sarcolipin as the basis for muscle non-shivering thermogenesis . Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences . 375 . 1793 . 20190135 . March 2020 . 31928193 . 10.1098/rstb.2019.0135 . 7017432 .
5. Legendre LJ, Davesne D . The evolution of mechanisms involved in vertebrate endothermy . Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences . 375 . 1793 . 20190136 . March 2020 . 31928191 . 10.1098/rstb.2019.0136 . 7017440 . free .
6. Reilly SM, Saltiel RA . A Futile Approach to Fighting Obesity? . Cell . 163 . 3 . 539–540 . 22 October 2015 . 10.1016/j.cell.2015.10.006 . 26496598 . 10336243 . free .
7. Asahi M, Sugita Y, Kurzydlowski K, De Leon S, Tada M, Toyoshima C, MacLennan DH . Sarcolipin regulates sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) by binding to transmembrane helices alone or in association with phospholamban . Proceedings of the National Academy of Sciences of the United States of America . 100 . 9 . 5040–5 . April 2003 . 12692302 . 154294 . 10.1073/pnas.0330962100 . 2003PNAS..100.5040A . free .
8. Asahi M, Kurzydlowski K, Tada M, MacLennan DH . Sarcolipin inhibits polymerization of phospholamban to induce superinhibition of sarco(endo)plasmic reticulum Ca2+-ATPases (SERCAs) . The Journal of Biological Chemistry . 277 . 30 . 26725–8 . July 2002 . 12032137 . 10.1074/jbc.C200269200 . free .