An Overview of Endoplasmic Reticulum Calpain System

  • Krishna Samanta
  • Pulak Kar
  • Tapati Chakraborti
  • Sajal Chakraborti
Part of the Advances in Biochemistry in Health and Disease book series (ABHD, volume 7)


Calpains, a family of Ca2+-dependent cysteine proteases, can modulate their substrates structure and function through limited proteolytic activity. Calpain mediated proteolysis of intracellular proteins is a key step in various cellular processes such as cytoskeleton modulation, cell migration, cell cycle progression and apoptosis. Calpain activity is controlled in vivo by calpastatin, a multiheaded endogenous polypeptide encoded by the calpastatin gene that specifically inhibits calpain. Calpains have previously been considered as the cytoplasmic enzymes; however, recent research have demonstrated that m-calpain and calpastatin are present in endoplasmic reticulum and play important roles in a variety of pathophysiological conditions including necrotic and apoptotic cell death phenomena. This review summarizes function and regulation of the endoplasmic reticulum calpain system, focusing on the relevance of its roles in several cellular and biochemical events under normal and some pathophysiological conditions.


Endoplasmic reticulum Calcium m-calpain Calpastatin Apoptosis 



Thanks are due to the University of Kalyani, Kalyani 741235, West Bengal, India for financial assistance.


  1. 1.
    Guroff G (1964) A neutral calcium-activated proteinase from the soluble fraction of rat brain. J Biol Chem 239:149–155PubMedGoogle Scholar
  2. 2.
    Huang Y, Wang KK (2001) The calpain family and human disease. Trends Mol Med 7:355–362PubMedCrossRefGoogle Scholar
  3. 3.
    Sorimachi H, Ishiura S, Suzuki K (1997) Structure and physiological function of calpains. Biochem J 328:721–732PubMedGoogle Scholar
  4. 4.
    Melloni E, Michetti M, Salamino F, Minafra R, Pontremoli S (1996) Modulation of the calpain autoproteolysis by calpastatin and phospholipids. Biochem Biophys Res Commun 229:193–197PubMedCrossRefGoogle Scholar
  5. 5.
    Nishimura T, Goll DE (1991) Binding of calpain fragments to calpastatin. J Biol Chem 266:1842–11850Google Scholar
  6. 6.
    Zhang S, Yuan JXJ, Barrett EK, Dong H (2005) Role of Na+/Ca2+ exchange in regulating cytosolic Ca2+ in cultured human pulmonary artery smooth muscle cells. Am J Physiol 288:C245–C252CrossRefGoogle Scholar
  7. 7.
    Bertram R, Arceo R (2008) A mathematical study of the differential effects of two SERCA isoforms on oscillation in pancreatic islet. Bull Math Biol 70:1251–1271PubMedCrossRefGoogle Scholar
  8. 8.
    Eva S, Una F, Afshin S (2003) Caspase -12 and ER- stress-mediated apoptosis the story so far. Ann N Y Acad Sci 1010:186–194CrossRefGoogle Scholar
  9. 9.
    Michalak M, Cobett EF, Mesaeli N, Nakamura K, Opas M (1999) Calreticulin: one protein, one gene, many functions. Biochem J 344:281–292PubMedCrossRefGoogle Scholar
  10. 10.
    Barnoy S, Zipser Y, Glaser T, Grimberg Y, Kosower NS (1999) Association of calpain (Ca dependent thiol protease) with its endogenous inhibitor calpastatin in myoblasts. J Cell Biochem 74:522–531PubMedCrossRefGoogle Scholar
  11. 11.
    Unlap MT, Bates E, Williams C, Komlosi P, Williams I, Siroky G, Siroky B, Bell PD (2003) Na+/Ca2+ exchanger: target for oxidative stress in salt-sensitive hypertension. Hypertension 42:363–368PubMedCrossRefGoogle Scholar
  12. 12.
    Letavernier E, Zafrani L, Letavernier B, Haymann JP, Baud L (2012) The role of calpains in myocardial remodeling and heart failure. Cardiovasc Res 96:38–45PubMedCrossRefGoogle Scholar
  13. 13.
    Ghosh SK, Chakraborti T, Michael JR, Chakraborti S (1996) Oxidant-mediated proteolytic activation of Ca2+ATPase in microsomes of pulmonary smooth muscle. FEBS Lett 387:171–174PubMedCrossRefGoogle Scholar
  14. 14.
    Chakraborti T, Ghosh SK, Michael JR, Chakraborti S (1996) Role of an aprotinin-sensitive protease in the activation of Ca2+-ATPase by superoxide radical in microsomes of pulmonary vascular smooth muscle. Biochem J 317:885–890PubMedGoogle Scholar
  15. 15.
    Goll DE, Thompson VF, Li H, Wei W, Cong J (2003) The calpain system. Physiol Rev 83:731–801PubMedGoogle Scholar
  16. 16.
    Smith MA, Schnellmann RG (2012) Calpains, mitochondria, and apoptosis. Cardiovasc Res 96(1):32–37PubMedCrossRefGoogle Scholar
  17. 17.
    Sorimachi H, Imajoh-Ohmi S, Emori Y, Kawasaki H, Ohno S, Minami Y et al (1989) Molecular cloning of a novel mammalian calcium-dependent protease distinct from both m- and mu-types Specific expression of the mRNA in skeletal muscle. J Biol Chem 264:20106–20111PubMedGoogle Scholar
  18. 18.
    Dear N, Matena K, Vingron M, Boehm T (1997) A new subfamily of vertebrate calpains lacking a calmodulin-like domain: implications for calpain regulation and evolution. Genomics 45:175–184PubMedCrossRefGoogle Scholar
  19. 19.
    Sorimachi H, Ishiura S, Suzuki K (1993) A novel tissue-specific calpain species expressed predominantly in the stomach comprises two alternative splicing products with and without Ca2+-binding domain. J Biol Chem 268:19476–19482PubMedGoogle Scholar
  20. 20.
    Dear TN, Boehm T (2001) Identification and characterization of two novel calpain large subunit genes. Gene 274:245–252PubMedCrossRefGoogle Scholar
  21. 21.
    Dear TN, Möller A, Boehm T (1999) CAPN11: a calpain with high mRNA levels in testis and located on chromosome 6 Genomics 59: 243-247Google Scholar
  22. 22.
    Dear TN, Meier NT, Hunn M, Boehm T (2000) Gene structure, chromosomal localization, and expression pattern of capn12, a new member of the calpain large subunit gene family. Genomics 68:152–160PubMedCrossRefGoogle Scholar
  23. 23.
    Suzuki K, Hata S, Kawabata Y, Sorimachi H (2004) Structure, activation, and biology of calpain. Diabetes 53:S12–S18PubMedCrossRefGoogle Scholar
  24. 24.
    Zatz M, Starling A (2005) Calpains and disease. New Eng J Med 352:2413–2423PubMedCrossRefGoogle Scholar
  25. 25.
    Wu HY, Tomizawa K, Matsui H (2007) calpain-calcineurin signaling in the pathogenesis of calcium-dependent disorder. Acta Med Okayama 61:123–137PubMedGoogle Scholar
  26. 26.
    Arrington DD, Van Vleet TR, Schnellmann RG (2006) Calpain 10: a mitochondrial calpain and its role in calcium-induced mitochondrial dysfunction Am J Physiol l291: C1159-C1171Google Scholar
  27. 27.
    Reverter D, Braun M, Fernandez-Catalan C, Strobl S, Sorimachi H, Bode W (2002) Flexibility analysis and structure comparison of two crystal forms of calcium-free human m-calpain. Biol Chem 383:1415–1422PubMedCrossRefGoogle Scholar
  28. 28.
    Moldoveanu T, Hosfield CM, Lim D, Elce JS, Jia Z, Davies PL (2002) A Ca2+ switch aligns the active site of calpain. Cell 108:649–660PubMedCrossRefGoogle Scholar
  29. 29.
    Tompa P, Emori Y, Sorimachi H, Suzuki K, Friedrich P (2001) Domain III of calpain is a Ca2+-regulated phospholipid-binding domain. Biochem Biophys Res Commun 280:1333–1339PubMedCrossRefGoogle Scholar
  30. 30.
    Strobl S, Fernandez-Catalan C, Braun M, Huber R, Masumoto H, Nakagawa K et al (2000) The crystal structure of calcium-free human m-calpain suggests an electrostatic switch mechanism for activation by calcium. Proc Natl Acad Sci U S A 97:588–592PubMedCrossRefGoogle Scholar
  31. 31.
    Kinbara K, Sorimachi H, Ishiura S, Suzuki K (1997) Muscle-specific calpain, p94, interacts with the extreme c-terminal region of connectin, a unique region flanked by two immunoglobulin C2 motifs. Arch Biochem Biophys 342:99–107PubMedCrossRefGoogle Scholar
  32. 32.
    Friedrich P, Papp H, Halasy K, Farkas A, Farkas B, Tompa P et al (2004) Differential distribution of calpain small subunit 1 and 2 in rat brain. Eur J Neurosci 19:1819–1825PubMedCrossRefGoogle Scholar
  33. 33.
    Sorimachi H, Suzuki K (2001) The structure of calpain. J Biochem 129:653–664PubMedCrossRefGoogle Scholar
  34. 34.
    Wendt A, Thompson VF, Goll DE (2004) Interaction of calpastatin with calpain: a review. Biol Chem 385:465–472PubMedCrossRefGoogle Scholar
  35. 35.
    Kawasaki H, Emori Y, Imajoh-Ohmi S, Minami Y, Suzuki K (1989) Identification and characterization of inhibitory sequences in four repeating domains of the endogenous inhibitor for calcium-dependent protease. J Biochem 106:274–281PubMedGoogle Scholar
  36. 36.
    Cong M, Thompson VF, Goll DE, Antin PB (1998) The bovine calpastatin gene promoter and a new N-terminal region of the protein are targets for cAMP-dependent protein kinase activity. J Biol Chem 273:660–666PubMedCrossRefGoogle Scholar
  37. 37.
    Kapprell HP, Goll DE (1989) Effect of Ca2+ on binding of the calpains to calpastatin. J Biol Chem 264:17888–17896PubMedGoogle Scholar
  38. 38.
    Kumamoto T, Kleese WC, Cong J, Goll DE, Pierce PR, Allen RE (1992) Localization of the Ca2+dependent proteinases and their inhibitor in normal, fasted, and denervated rat skeletal muscle Ana Res 232: 60–77Google Scholar
  39. 39.
    Goll DE, Thompson VF, Taylor RG, Zalewska T (1992) Is calpain activity regulated by membranes and autolysis or by calcium and calpastatin? Bioessays 14:549–556PubMedCrossRefGoogle Scholar
  40. 40.
    Shaikh S, Samanta K, Kar P, Roy S, Chakraborti T, Chakraborti S (2010) m-Calpain-mediated cleavage of Na+/Ca2+ exchanger-1 in caveolae vesicles isolated from pulmonary artery smooth muscle. Mol Cell Biochem 341:167–180PubMedCrossRefGoogle Scholar
  41. 41.
    Kar P, Samanta K, Shaikh S, Chowdhury A, Chakraborti T, Chakraborti S (2010) Mitochondrial calpain system: an overview. Arch Biochem Biophys 495:1–7PubMedCrossRefGoogle Scholar
  42. 42.
    Samanta K, Kar P, Ghosh B, Chakraborti T, Chakraborti S (2007) Localization of m-calpain and calpastatin and studies of their association in pulmonary smooth muscle endoplasmic reticulum. Biochem Biophys Acta 1770:1297–1307PubMedCrossRefGoogle Scholar
  43. 43.
    Hood JL, Logan BB, Sinai AP, Brooks WH, Roszman TL (2003) Association of the calpain/calpastatin network with subcellular organelles. Biochem Biophys Res Commun 310: 1200–1212PubMedCrossRefGoogle Scholar
  44. 44.
    Honda S, Marumoto T, Hirota T, Nitta M, Arima Y, Ogawa M, Saya H (2004) Activation of m-calpain is required for chromosome alignment on the metaphase plate during mitosis. J Biol Chem 279:10615–10623PubMedCrossRefGoogle Scholar
  45. 45.
    Samanta K, Kar P, Chakraborti T, Shaikh S, Chakraborti S (2010) Characteristic properties of endoplasmic reticulum membrane m-calpain, calpastatin and lumen m-calpain: a comparative study between membrane and lumen m-calpains. J Biochem 147:765–779PubMedCrossRefGoogle Scholar
  46. 46.
    Edmunds T, Naganis PA, Sathe SK, Thompson VF, Goll DE (1991) Comparison of the autolyzed and unautolyzed forms of μ-and m-calpain from bovine skeletal muscle. Biochim Biophys Acta 1077:197–208PubMedCrossRefGoogle Scholar
  47. 47.
    Hood JL, Brooks WH, Roszman TL (2004) Differential compartmentalization of the calpain/calpastatin network with the endoplasmic reticulum and Golgi apparatus. J Biol Chem 278:43126–43135CrossRefGoogle Scholar
  48. 48.
    Hosfield CM, Moldoveanu T, Davies PL, Elce JS, Jia Z (2001) Calpain mutants with increased Ca2+ sensitivity and implications for the role of the C(2)-like domain. J Biol Chem 276:7404–7407PubMedCrossRefGoogle Scholar
  49. 49.
    Evans JH, Gerger SH, Murray D, Leslie C (2004) The calcium binding loops of the cytosolic phospholipase A2 C2 domain specify targeting to Golgi and ER in live cells. Mol Biol Cell 15:371–383PubMedCrossRefGoogle Scholar
  50. 50.
    Xie X, Dwyer MD, Swenson L, Parker MH, Botfield MC (2001) Crystal structure of calcium-free human sorcin: a member of the penta-EF-hand protein family. Protein Sci 10:2419–2425PubMedCrossRefGoogle Scholar
  51. 51.
    Nishihara H, Nakagawa Y, Ishikawa H, Ohba M, Shimizu K, Nakamura T (2001) Matrix vesicles and media vesicle as nonclassical pathways for the secretion of m-calpain from MC3T3-E1 cells. Biochem Biophys Res Commun 285:845–853PubMedCrossRefGoogle Scholar
  52. 52.
    Tam LY, Loo TW, Clarke DM, Reithmeier AF (1994) Identification of an internal topogenic signal sequence in human Band 3, the erythrocyte anion exchanger. J Biol Chem 269:32542–32550PubMedGoogle Scholar
  53. 53.
    Joliot A, Maizel A, Rosenberg D, Trembleau A, Dupas S, Volovitch M, Prochiantz A (1998) Identification of a signal sequence necessary for the unconventional secretion of Engrailed homeoprotein. Curr Biol 8:856–863PubMedCrossRefGoogle Scholar
  54. 54.
    Samanta K, Kar P, Chakraborti T, Chakrabort S (2010) Calcium-dependent cleavage of the Na+/Ca2+ exchanger by m-calpain in isolated endoplasmic reticulum. J Biochem 147:225–235PubMedCrossRefGoogle Scholar
  55. 55.
    Takano J, Watanabe M, Hitomi K, Maki M (2000) Four types of calpastatin isoforms with distinct ammo-terminal sequences are specified by alternative first exons and differentially expressed in mouse tissues. J Biochem 128:83–92PubMedCrossRefGoogle Scholar
  56. 56.
    Ozaki T, Yamashita T, Ishiguro S (2009) Mitochondrial m-calpain plays a role in the release of truncated apoptosis-inducing factor from the mitochondria. Biochim Biophys Acta 1793: 1848–1859PubMedCrossRefGoogle Scholar
  57. 57.
    Ozaki T, Yamashita T, Ishiguro S (2008) ERp57-associated mitochondrial micro-calpain truncates apoptosis-inducing factor. Biochim Biophys Acta 1783:1955–1963PubMedCrossRefGoogle Scholar
  58. 58.
    Xu D, Perez RE, Rezaiekhaligh MH, Bourdi M, Truog WE (2009) Knockdown of ERp57 increases BiP/GRP78 induction and protects against hyperoxia and tunicamycin-induced apoptosis. Am J Physiol Lung Cell Mol Physiol 297:L44–L51PubMedCrossRefGoogle Scholar
  59. 59.
    Prins D, Michalak M (2009) Endoplasmic reticulum proteins in cardiac development and dysfunction. Can J Physiol Pharmacol 87:419–425PubMedCrossRefGoogle Scholar
  60. 60.
    Michalak M, Groendyk J, Szabo E, Gold LI, Opas M (2009) Calreticulin, a multi-process calcium-buffering chaperone of the endoplasmic reticulum. Biochem J 417:651–666PubMedCrossRefGoogle Scholar
  61. 61.
    Laporte R, Hui A, Laher I (2004) Pharmacological modulation of sarcoplasmic reticulum function in smooth muscle. Pharmacol Rev 56:439–513PubMedCrossRefGoogle Scholar
  62. 62.
    Chakraborti S, Mandal A, Das S, Chakraborti T (2004) Inhibition of Na+/Ca2+- exchanger by peroxynitrite in microsomes of pulmonary smooth muscle: role of matrix metalloproteinase-2 Biochim Biophys Acta 1671: 70-78Google Scholar
  63. 63.
    Case RM, Eisner D, Gurney A, Jones O, Muallemd S, Verkhratsky A (2007) Evolution of calcium homeostasis: from birth of the first cell to an omnipresent signaling system. Cell Calcium 42:345–350PubMedCrossRefGoogle Scholar
  64. 64.
    Takano J, Tomioka M, Tsubuki S, Higuchi M, Iwata N, Itohara S, Maki M, Saido TC (2005) Calpain mediates excitotoxic DNA fragmentation via mitochondrial pathways in adult brains. J Biol Chem 280:16175–16184PubMedCrossRefGoogle Scholar
  65. 65.
    Nicotera P, Hartzell P, Baldi C, Svensson SA, Bellomo G, Orrenius S (1986) Cystamine induces toxicity in hepatocytes through the elevation of cytosolic Ca2+ and the stimulation of a nonlysosomal proteolytic system. J Biol Chem 261:14628–14635PubMedGoogle Scholar
  66. 66.
    Rardon DP, Cefali DC, Mitchell RD, Seiler SM, Hathaway DR, Jones LR (1990) Digestion of cardiac and skeletal muscle junctional sarcoplasmic reticulum vesicles with calpain II Effects on the Ca2+ release channel. Circ Res 67:84–96PubMedCrossRefGoogle Scholar
  67. 67.
    Igwe OJ, Filla MB (1997) Aging-related regulation of myoinositol 1,4,5-trisphosphate signal transduction pathway in the rat striatum. Brain Res Mol Brain Res 46:39–53PubMedCrossRefGoogle Scholar
  68. 68.
    Bevers BM, Neumar WR (2008) Mechanistic role of calpains in postischemic neurodegeneration. J Cereb Blood Flow Metab 28:655–673PubMedCrossRefGoogle Scholar
  69. 69.
    French JP, Quindry JC, Falk DJ, Staib JL, Lee Y, Wang KK, Powers SK (2006) Ischemia–reperfusion-induced calpain activation and SERCA2a degradation are attenuated by exercise training and calpain inhibition. Am J Physiol 290:H128–H136Google Scholar
  70. 70.
    Parsons JT, Churn SB, DeLorenzo RJ (1999) Global ischemia-induced inhibition of the coupling ratio of calcium uptake and ATP hydrolysis by rat whole brain microsomal Mg2+/Ca2+ ATPase. Brain Res 834:32–41PubMedCrossRefGoogle Scholar
  71. 71.
    Davis KA, Samson SE, Hammel KE, Kiss L, Fulop F, Grover AK (2008) Functional linkage of Na+/Ca2+-exchanger to sarco/endoplasmic reticulum Ca2+ pump in coronary artery: comparison of smooth muscle and endothelial cells. J Cell Mol Med 12:1–9Google Scholar
  72. 72.
    Farrukh IS, Michael JR, Summer WR, Adkinson NF, Gurtner GH (1985) Thromboxane induced pulmonary vasoconstriction: involvement of calcium. J Appl Physiol 58:34–44PubMedGoogle Scholar
  73. 73.
    Lam M, Dubyak G, Chen L, Nunez G, Miesfeld RL, Distel-horst CW (1994) Evidence that BCL-2 represses apoptosis by regulating endoplasmic reticulum-associated Ca2+ fluxes Proc Natl Acad Sci (USA) 91: 6569–6573Google Scholar
  74. 74.
    Pinton P, Ferrari D, Magalhaes P, Schulze-Osthoff K, Di Virgilio F, Pozzan T, Rizzuto R (2000) Reduced loading of intracellular Ca2+ stores and downregulation of capacitative Ca2+ influx in Bcl-2-overexpressing cells. J Cell Biol 148:857–862PubMedCrossRefGoogle Scholar
  75. 75.
    Scorrano L, Oakes SA, Opferman JT, Cheng EH, Sorcinelli MD, Pozzan T, Korsmeyer SJ (2003) BAX and BAK regula- tion of endoplasmic reticulum Ca2+: a control point for apoptosis Science 300: 135–139Google Scholar
  76. 76.
    Danial NN, Korsmeyer SJ (2004) Cell death: critical control points. Cell 116:205–219PubMedCrossRefGoogle Scholar
  77. 77.
    Vermeulen K, Bockstaele DRV, Berneman ZN (2005) Apoptosis: mechanisms and relevance in cancer. Ann Hematol 84:627–639PubMedCrossRefGoogle Scholar
  78. 78.
    Rasheva VI, Domingos PM (2009) Cellular responses to endoplasmic reticulum stress and apoptosis. Apoptosis 14:996–1007PubMedCrossRefGoogle Scholar
  79. 79.
    Moshal KS, Singh M, Sen U, Rosenberger DSE, Henderson B, Tyagi N et al (2006) Homocysteine-mediated activation and mitochondrial translocation of calpain regulates MMP-9 in MVEC. Am J Physiol Heart Circ Physiol 291:H2825–H2835PubMedCrossRefGoogle Scholar
  80. 80.
    Papatheodorou L, Weiss N (2007) Vascular Oxidant Stress and Inflammation in Hyperhomocysteinemia. Antioxid Redox Signal 9:1941–1958PubMedCrossRefGoogle Scholar
  81. 81.
    Roberts-Lewis JM, Savage MJ, Marcy VR, Pinsker LR, Siman R (1994) Immunolocalization of calpain I-mediated spectrin degradation to vulnerable neurons in the ischemic gerbil brain. J Neurosci 14:3934–3944PubMedGoogle Scholar
  82. 82.
    Wei H, Perry DC (1996) Dantrolene is cytoprotective in two models of neuronal cell death. J Neurochem 67:2390–2398PubMedCrossRefGoogle Scholar
  83. 83.
    Nakayama R, Yano T, Ushijima K, Abe E, Terasaki H (2002) Effects of dantrolene on extracellular glutamate concentration and neuronal death in the rat hippocampal CA1 region subjected to transient ischemia. Anesthesiology 96:705–710PubMedCrossRefGoogle Scholar
  84. 84.
    Kopil CM, Siebert AP, Kevin Foskett J, Neumar RW (2012) Calpain-cleaved type 1 inositol 1,4,5-trisphosphate receptor impairs ER Ca2+ buffering and causes neurodegeneration in primary cortical neurons. J Neurochem 123:147–158PubMedCrossRefGoogle Scholar
  85. 85.
    Kopil CM, Vais H, Cheung KH, Siebert AP, Mak DO, Foskett JK, Neumar RW (2011) Calpain-cleaved type 1 inositol 1,4,5-trisphosphate receptor (InsP(3)R1) has InsP(3)-independent gating and disrupts intracellular Ca2+ homeostasis. J Biol Chem 286:35998–36010PubMedCrossRefGoogle Scholar
  86. 86.
    Mattson MP (2000) Apoptosis in neurodegenerative disorders. Nat Rev Mol Cell Biol 1:120–129PubMedCrossRefGoogle Scholar
  87. 87.
    Kaufman RJ (1999) Stress signaling from the lumen of the endo-plasmic reticulum: coordination of gene transcriptional and translational controls. Genes Dev 13:1211–1233PubMedCrossRefGoogle Scholar
  88. 88.
    Sorimachi H, Ono Y (2012) Regulation and physiological roles of the calpain system in muscular disorders. Cardiovasc Res 96:11–22PubMedCrossRefGoogle Scholar
  89. 89.
    Müller AL, Hryshko LV, Dhalla NS (2012) Extracellular and intracellular proteases in cardiac dysfunction due to ischemia–reperfusion injury. Int J Cardiol 164(1):39–47PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Krishna Samanta
    • 1
  • Pulak Kar
    • 1
  • Tapati Chakraborti
    • 2
  • Sajal Chakraborti
    • 2
  1. 1.Department of Physiology, Anatomy and GeneticsUniversity of OxfordOxfordUK
  2. 2.Department of Biochemistry and BiophysicsUniversity of KalyaniKalyaniIndia

Personalised recommendations