Sorcin interacts with sarcoplasmic reticulum Ca2+–ATPase and modulates excitation–contraction coupling in the heart
Tóm tắt
Sorcin is a 21.6–kDa Ca2+ binding protein of the penta–EF hand
family. Several studies have shown that sorcin modulates multiple proteins
involved in excitation–contraction (E–C) coupling in the heart, such as the
cardiac ryanodine receptor (RyR2), L–type Ca2+ channel, and Na+–Ca2+
exchanger, while it has also been shown to be phosphorylated by cAMP–dependent
protein kinase (PKA). To elucidate the effects of sorcin and its
PKA–dependent regulation on E–C coupling in the heart, we identified the
PKA–phosphorylation site of sorcin, and found that serine178 was preferentially
phosphorylated by PKA and dephosphorylated by protein phosphatase–
1. Isoproterenol allowed sorcin to translocate to the sarcoplasmic reticulum
(SR). In addition, adenovirus–mediated overexpression of sorcin in adult rat
cardiomyocytes significantly increased both the rate of decay of the Ca2+
transient and the SR Ca2+ load. An assay of oxalate–facilitated Ca2+ uptake
showed that recombinant sorcin increased Ca2+ uptake in a dose–dependent
manner. These data suggest that sorcin activates the Ca2+–uptake function in
the SR. In UM–X7. 1 cardiomyopathic hamster hearts, the relative amount of
sorcin was significantly increased in the SR fraction, whereas it was significantly decreased in whole–heart homogenates. In failing hearts, PKA–phosphorylated
sorcin was markedly increased, as assessed using a back–phosphorylation
assay with immunoprecipitated sorcin. Our results suggest that
sorcin activates Ca2+–ATPase–mediated Ca2+ uptake and restores SR Ca2+
content, and may play critical roles in compensatory mechanisms in both
Ca2+ homeostasis and cardiac dysfunction in failing hearts.
Tài liệu tham khảo
Baartscheer A, Schumacher CA, Belterman CN, Coronel R, Fiolet JW (2003) SR calcium handling and calcium after-transients in a rabbit model of heart failure. Cardiovasc Res 58:99–108
Bers DM (2002) Cardiac excitation-contraction coupling. Nature 415:198–205
Bond M, Jaraki AR, Disch CH, Healy BP (1989) Subcellular calcium content in cardiomyopathic hamster hearts in vivo: an electron probe study. Circ Res 64:1001–1012
Callewaert G, Cleemann L, Morad M (1988) Epinephrine enhances Ca2+ current- regulated Ca2+ release and Ca2+ reuptake in rat ventricular myocytes. Proc Natl Acad Sci USA 85:2009–2013
Fabiato A (1983) Calcium-induced release of calcium from the cardiac sarcoplasmic reticulum. Am J Physiol 245:C1–C14
Farrell EF, Antaramian A, Rueda A, Gomez AM, Valdivia HH (2003) Sorcin inhibits calcium release and modulates excitation-contraction coupling in the heart. J Biol Chem 278:34660–34666
Gerhardstein BL, Puri TS, Chien AJ, Hosey MM (1999) Identification of the sites phosphorylated by cyclic AMP-dependent protein kinase on the beta 2 subunit of L-type voltage-dependent calcium channels. Biochemistry 38:10361–10370
Guatimosim S, Dilly K, Santana LF, Saleet Jafri M, Sobie EA, Lederer WJ (2002) Local Ca(2+) signaling and EC coupling in heart: Ca(2+) sparks and the regulation of the [Ca(2+)](i) transient. J Mol Cell Cardiol 34:941–950
Hano O, Lakatta EG (1991) Diminished tolerance of prehypertrophic, cardiomyopathic Syrian hamster hearts to Ca2+ stresses. Circ Res 69:123–133
Hasenfuss G, Pieske B (2002) Calcium cycling in congestive heart failure. J Mol Cell Cardiol 34:951–969
Hisamatsu Y, Ohkusa T, Kihara Y, Inoko M, Ueyama T, Yano M, Sasayama S, Matsuzaki M (1997) Early changes in the functions of cardiac sarcoplasmic reticulum in volume-overloaded cardiac hypertrophy in rats. J Mol Cell Cardiol 29:1097–1109
Hobai IA, O’Rourke B (2001) Decreased sarcoplasmic reticulum calcium content is responsible for defective excitationcontraction coupling in canine heart failure. Circulation 103:1577–1584
Ilari A, Johnson KA, Nastopoulos V, Verzili D, Zamparelli C, Colotti G, Tsernoglou D, Chiancone E (2002) The crystal structure of the sorcin calcium binding domain provides a model of Ca2+-dependent processes in the fulllength protein. J Mol Biol 317:447–458
Itaya K, Ui M (1966) A new micromethod for the colorimetric determination of inorganic phosphate. Clin Chim Acta 14:361–366
Iwanaga Y, Kihara Y, Yoneda T, Aoyama T, Sasayama S (2000) Modulation of in vivo cardiac hypertrophy with insulinlike growth factor-1 and angiotensinconverting enzyme inhibitor: relationship between change in myosin isoform and progression of left ventricular dysfunction. J Am Coll Cardiol 36:635–642
Lanzetta PA, Alvarez LJ, Reinach PS, Candia OA (1979) An improved assay for nanomole amounts of inorganic phosphate. Anal Biochem 100:95–97
Lokuta AJ, Meyers MB, Sander PR, Fishman GI, Valdivia HH (1997) Modulation of cardiac ryanodine receptors by sorcin. J Biol Chem 272:25333–25338
Maki M, Kitaura Y, Satoh H, Ohkouchi S, Shibata H (2002) Structures, functions and molecular evolution of the penta-EF-hand Ca2+-binding proteins. Biochim Biophys Acta 1600:51–60
Marx SO, Reiken S, Hisamatsu Y, Jayaraman T, Burkhoff D, Rosemblit N, Marks AR (2000) PKA phosphorylation dissociates FKBP12. 6 from the calcium release channel (ryanodine receptor): defective regulation in failing hearts. Cell 101:365–376
Marx SO, Reiken S, Hisamatsu Y, Gaburjakova M, Gaburjakova J, Yang YM, Rosemblit N, Marks AR (2001) Phosphorylation-dependent regulation of ryanodine receptors: a novel role for leucine/isoleucine zippers. J Cell Biol 153:699–708
Mella M, Colotti G, Zamparelli C, Verzili D, Ilari A, Chiancone E (2003) Information transfer in the penta-EF-hand protein sorcin does not operate via the canonical structural/functional pairing. A study with site-specific mutants. J Biol Chem 278:24921–24928
Meyers MB, Pickel VM, Sheu SS, Sharma VK, Scotto KW, Fishman GI (1995) Association of sorcin with the cardiac ryanodine receptor. J Biol Chem 270:26411–26418
Meyers MB, Zamparelli C, Verzili D, Dicker AP, Blanck TJ, Chiancone E (1995) Calcium-dependent translocation of sorcin to membranes: functional relevance in contractile tissue. FEBS Lett 357:230–234
Meyers MB, Fischer A, Sun YJ, Lopes CM, Rohacs T, Nakamura TY, Zhou YY, Lee PC, Altschuld RA, McCune SA, Coetzee WA, Fishman GI (2003) Sorcin regulates excitation-contraction coupling in the heart. J Biol Chem 278:28865–28871
Pearson RB, Kemp BE (1991) Protein kinase phosphorylation site sequences and consensus specificity motifs: tabulations. Methods Enzymol 200:62–81
Remppis A, Most P, Loffler E, Ehlermann P, Bernotat J, Pleger S, Borries M, Reppel M, Fischer J, Koch WJ, Smith G, Katus HA (2002) The small EF-hand Ca2+ binding protein S100A1 increases contractility and Ca2+ cycling in rat cardiac myocytes. Basic Res Cardiol 97 (Suppl 1):I56–I62
Schmidt U, Hajjar RJ, Helm PA, Kim CS, Doye AA, Gwathmey JK (1998) Contribution of abnormal sarcoplasmic reticulum ATPase activity to systolic and diastolic dysfunction in human heart failure. J Mol Cell Cardiol 30:1929–1937
Schmidt U, Hajjar RJ, Kim CS, Lebeche D, Doye AA, Gwathmey JK (1999) Human heart failure: cAMP stimulation of SR Ca(2+)-ATPase activity and phosphorylation level of phospholamban. Am J Physiol 277:H474–H480
Seidler T, Miller SL, Loughrey CM, Kania A, Burow A, Kettlewell S, Teucher N, Wagner S, Kogler H, Meyers MB, Hasenfuss G, Smith GL (2003) Effects of adenovirus- mediated sorcin overexpression on excitation-contraction coupling in isolated rabbit cardiomyocytes. Circ Res 93:132–139
Simmerman HK, Jones LR (1998) Phospholamban: protein structure, mechanism of action, and role in cardiac function. Physiol Rev 78:921–947
Sjaastad I, Wasserstrom JA, Sejersted OM (2003) Heart failure – a challenge to our current concepts of excitation-contraction coupling. J Physiol 546:33–47
Smith JS, Rousseau E, Meissner G (1989) Calmodulin modulation of single sarcoplasmic reticulum Ca2+-release channels from cardiac and skeletal muscle. Circ Res 64:352–359
Suarez J, Belke DD, Gloss B, Dieterle T, McDonough PM, Kim YK, Brunton LL, Dillmann WH (2004) In vivo adenoviral transfer of sorcin reverses cardiac contractile abnormalities of diabetic cardiomyopathy. Am J Physiol Heart Circ Physiol 286:H68–H75
Tada M (2003) Calcium cycling proteins of the cardiac sarcoplasmic reticulum. Circ J 67:729–737
Takasago T, Imagawa T, Shigekawa M (1989) Phosphorylation of the cardiac ryanodine receptor by cAMP-dependent protein kinase. J Biochem (Tokyo) 106:872–877
Ueyama T, Ohkusa T, Hisamatsu Y, Nakamura Y, Yamamoto T, Yano M, Matsuzaki M (1998) Alterations in cardiac SR Ca(2+)-release channels during development of heart failure in cardiomyopathic hamsters. Am J Physiol 274:H1–H7
Wei SK, Ruknudin A, Hanlon SU, McCurley JM, Schulze DH, Haigney MC (2003) Protein kinase A hyperphosphorylation increases basal current but decreases beta-adrenergic responsiveness of the sarcolemmal Na+-Ca2+ exchanger in failing pig myocytes. Circ Res 92:897–903
Zhao XL, Gutierrez LM, Chang CF, Hosey MM (1994) The alpha 1-subunit of skeletal muscle L-type Ca channels is the key target for regulation by A-kinase and protein phosphatase-1C. Biochem Biophys Res Commun 198:166–173
Zhou YY, Wang SQ, Zhu WZ, Chruscinski A, Kobilka BK, Ziman B, Wang S, Lakatta EG, Cheng H, Xiao RP (2000) Culture and adenoviral infection of adult mouse cardiac myocytes: methods for cellular genetic physiology. Am J Physiol Heart Circ Physiol 279:H429–H436