Frontiers of Medicine

, Volume 10, Issue 4, pp 397–404 | Cite as

Caveolin proteins: a molecular insight into disease

  • Hongli Yin
  • Tianyi Liu
  • Ying Zhang
  • Baofeng Yang


Caveolae are a kind of specific cystic structures of lipid rafts in the cytoplasmic membrane and are rich in cholesterol and sphingolipids. In recent years, many researchers have found that both caveolins and caveolae play a role in the development of various human diseases, including coronary heart disease, hypertension, and nervous system disorders. The specific mechanisms by which caveolins induce diseases have been a topic of interest. However, a number of detailed molecular mechanisms remain poorly understood. This article focuses on the relationship between caveolin proteins and human diseases and reviews the molecular mechanisms of caveolins in disease networks.


caveolin caveolae microRNA disease signaling pathway heart tumor 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Kiss AL, Aacute, Turig, Müller N, Kántor O, Botos E. Caveolae and caveolin isoforms in rat peritoneal macrophages. Micron 2002;33(1):75–93CrossRefPubMedGoogle Scholar
  2. 2.
    Parton RG. Caveolae and caveolins. Curr Opin Cell Biol 1996; 8(4): 542–548CrossRefPubMedGoogle Scholar
  3. 3.
    Sargiacomo M, Scherer PE, Tang Z, Kübler E, Song KS, Sanders MC, Lisanti MP. Oligomeric structure of caveolin: implications for caveolae membrane organization. Proc Natl Acad Sci USA 1995; 92(20): 9407–9411CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Okamoto T, Schlegel A, Scherer PE, Lisanti MP. Caveolins, a family of scaffolding proteins for organizing “preassembled signaling complexes” at the plasma membrane. J Biol Chem 1998; 273(10): 5419–5422CrossRefPubMedGoogle Scholar
  5. 5.
    Harris J, Werling D, Hope JC, Taylor G, Howard CJ. Caveolae and caveolin in immune cells: distribution and functions. Trends Immunol 2002; 23(3): 158–164CrossRefPubMedGoogle Scholar
  6. 6.
    Ockleford CD, Cairns H, Rowe AJ, Byrne S, Scott JJA, Willingale R. The distribution of caveolin-3 immunofluorescence in skeletal muscle fibre membrane defined by dual channel confocal laser scanning microscopy, fast Fourier transform and image modelling. J Microsc 2002; 206(Pt 2): 93–105CrossRefPubMedGoogle Scholar
  7. 7.
    Root KT, Plucinsky SM, Glover KJ. Recent progress in the topology, structure, and oligomerization of caveolin: a building block of caveolae. Curr Top Membr 2015; 75(6): 305–336CrossRefPubMedGoogle Scholar
  8. 8.
    Schubert W, Cohen AW, Hnasko R, Lisanti MP. Role of caveolae and caveolins in health and disease. Physiol Rev 2004;84(4):1341–1379CrossRefPubMedGoogle Scholar
  9. 9.
    Low JY, Nicholson HD. Epigenetic modifications of caveolae associated proteins in health and disease. BMC Genet 2015; 16(1): 71CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Boscher C, Nabi IR. Caveolin-1: Role in Cell Signaling. Springer US, 2012: 29–50Google Scholar
  11. 11.
    Han B, Tiwari A, Kenworthy AK. Tagging strategies strongly affect the fate of overexpressed caveolin-1. Traffic 2015; 16(4): 417–438CrossRefPubMedGoogle Scholar
  12. 12.
    Liu P, Rudick M, Anderson RG. Multiple functions of caveolin-1. J Biol Chem 2002; 277(44): 41295–41298CrossRefPubMedGoogle Scholar
  13. 13.
    Virgintino D, Robertson D, Errede M, Benagiano V, Tauer U, Roncali L, Bertossi M. Expression of caveolin-1 in human brain microvessels. Neuroscience 2002; 115(1): 145–152CrossRefPubMedGoogle Scholar
  14. 14.
    Arvanitis DN, Wang H, Bagshaw RD, Callahan JW, Boggs JM. Membrane-associated estrogen receptor and caveolin-1 are present in central nervous system myelin and oligodendrocyte plasma membranes. J Neurosci Res 2004; 75(5): 603–613CrossRefPubMedGoogle Scholar
  15. 15.
    Grossi M, Rippe C, Sathanoori R, Swärd K, Forte A, Erlinge D, Persson L, Hellstrand P, Nilsson BO. Vascular smooth muscle cell proliferation depends on caveolin-1-regulated polyamine uptake. Biosci Rep 2014;34(6):e00153CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Gu Y, Zheng G, Xu M, Li Y, Chen X, Zhu W, Tong Y, Chung SK, Liu KJ, Shen J. Caveolin-1 regulates nitric oxide-mediated matrix metalloproteinases activity and blood-brain barrier permeability in focal cerebral ischemia and reperfusion injury. J Neurochem 2012; 120(1): 147–156CrossRefPubMedGoogle Scholar
  17. 17.
    Chen Y, Dai Z, Liu YM, Tian HH, Deng SX, Chen LX, Wang HD, Qin XP. Inhibitory effects of CGRP on vascular smooth muscle cell proliferation: role of caveolae/caveolin-1/erk_(1/2) signal pathway. Acta Agron Sin 2013; 40(5): 445–453CrossRefGoogle Scholar
  18. 18.
    Grande-García A, del Pozo MA. Caveolin-1 in cell polarization and directional migration. Eur J Cell Biol 2008; 87(8-9): 641–647CrossRefPubMedGoogle Scholar
  19. 19.
    Jasmin JF, Malhotra S, Singh Dhallu M, Mercier I, Rosenbaum DM, Lisanti MP. Caveolin-1 deficiency increases cerebral ischemic injury. Circ Res 2007; 100(5): 721–729CrossRefPubMedGoogle Scholar
  20. 20.
    Li Y, Lau WM, So KF, Tong Y, Shen J. Caveolin-1 promote astroglial differentiation of neural stem/progenitor cells through modulating Notch1/NICD and Hes1 expressions. Biochem Biophys Res Commun 2011; 407(3): 517–524CrossRefPubMedGoogle Scholar
  21. 21.
    Sun JH, Yu JT, Tan L. The role of cholesterol metabolism in Alzheimer’s disease. Mol Neurobiol 2015; 51(3): 947–965CrossRefPubMedGoogle Scholar
  22. 22.
    Kuo YM, Beach TG, Sue LI, Scott S, Layne KJ, Kokjohn TA, Kalback WM, Luehrs DC, Vishnivetskaya TA, Abramowski D, Sturchler-Pierrat C, Staufenbiel M, Weller RO, Roher AE. The evolution of A β peptide burden in the APP23 transgenic mice: implications for A β deposition in Alzheimer disease. Mol Med 2001; 7(9): 609–618PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Kapoor A, Wang BJ, Liao YF. P3–334: γ-secretase–mediated proteolysis of APP and notch is regulated by caveolin-1. Alzheimer’s Dementia 2008; 4(4Suppl):T619–T620CrossRefGoogle Scholar
  24. 24.
    Cameron PL, Ruffin JW, Bollag R, Rasmussen H, Cameron RS. Identification of caveolin and caveolin-related proteins in the brain. J Neurosci 1997; 17(24): 9520–9535CrossRefPubMedGoogle Scholar
  25. 25.
    Gaudreault SB, Dea D, Poirier J. Increased caveolin-1 expression in Alzheimer’s disease brain. Neurobiol Aging 2004; 25(6): 753–759CrossRefPubMedGoogle Scholar
  26. 26.
    Head BP, Peart JN, Panneerselvam M, Yokoyama T, Pearn ML, Niesman IR, Bonds JA, Schilling JM, Miyanohara A, Headrick J, Ali SS, Roth DM, Patel PM, Patel HH. Loss of caveolin-1 accelerates neurodegeneration and aging. PLoS ONE 2010; 5(12): e15697CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Salgado IK, Serrano M, García JO, Martínez NA, Maldonado HM, Báez-Pagán CA, Lasalde-Dominicci JA, Silva WI. SorLA in glia: shared subcellular distribution patterns with caveolin-1. Cell Mol Neurobiol 2012; 32(3): 409–421CrossRefPubMedGoogle Scholar
  28. 28.
    Diaz-Valdivia N, Bravo D, Huerta H, Henriquez S, Gabler F, Vega M, Romero C, Calderon C, Owen GI, Leyton L, Quest AF. Enhanced caveolin-1 expression increases migration, anchorageindependent growth and invasion of endometrial adenocarcinoma cells. BMC Cancer 2015; 15(1): 463CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Hulit J, Bash T, Fu M, Galbiati F, Albanese C, Sage DR, Schlegel A, Zhurinsky J, Shtutman M, Ben-Ze’ev A, Lisanti MP, Pestell RG. The cyclin D1 gene is transcriptionally repressed by caveolin-1. J Biol Chem 2000; 275(28): 21203–21209CrossRefPubMedGoogle Scholar
  30. 30.
    Fiucci G, Ravid D, Reich R, Liscovitch M. Caveolin-1 inhibits anchorage-independent growth, anoikis and invasiveness in MCF-7 human breast cancer cells. Oncogene 2002; 21(15): 2365–2375CrossRefPubMedGoogle Scholar
  31. 31.
    Li S, Couet J, Lisanti MP. Src tyrosine kinases, G α subunits, and HRas share a common membrane-anchored scaffolding protein, caveolin. Caveolin binding negatively regulates the auto-activation of Src tyrosine kinases. J Biol Chem 1996; 271(46): 29182–29190CrossRefPubMedGoogle Scholar
  32. 32.
    Lee H, Park DS, Razani B, Russell RG, Pestell RG, Lisanti MP. Caveolin-1 mutations (P132L and null) and the pathogenesis of breast cancer: caveolin-1 (P132L) behaves in a dominant-negative manner and caveolin-1 (-/-) null mice show mammary epithelial cell hyperplasia. Am J Pathol 2002; 161(4): 1357–1369CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Lee H, Volonte D, Galbiati F, Iyengar P, Lublin DM, Bregman DB, Wilson MT, Campos-Gonzalez R, Bouzahzah B, Pestell RG, Scherer PE, Lisanti MP. Constitutive and growth factor-regulated phosphorylation of caveolin-1 occurs at the same site (Tyr-14) in vivo: identification of a c-Src/Cav-1/Grb7 signaling cassette. Mol Endocrinol 2000; 14(11): 1750–1775CrossRefPubMedGoogle Scholar
  34. 34.
    Kasper M, Seidel D, Knels L, Morishima N, Neisser A, Bramke S, Koslowski R. Early signs of lung fibrosis after in vitro treatment of rat lung slices with CdCl2 and TGF-β1. Histochem Cell Biol 2004; 121(2): 131–140CrossRefPubMedGoogle Scholar
  35. 35.
    Koslowski R, Barth K, Augstein A, Tschernig T, Bargsten G, Aufderheide M, Kasper M. A new rat type I-like alveolar epithelial cell line R3/1: bleomycin effects on caveolin expression. Histochem Cell Biol 2004; 121(6): 509–519CrossRefPubMedGoogle Scholar
  36. 36.
    Drab M, Verkade P, Elger M, Kasper M, Lohn M, Lauterbach B, Menne J, Lindschau C, Mende F, Luft FC, Schedl A, Haller H, Kurzchalia TV. Loss of caveolae, vascular dysfunction, and pulmonary defects in caveolin-1 gene-disrupted mice. Science 2001; 293(5539): 2449–2452CrossRefPubMedGoogle Scholar
  37. 37.
    Murata T, Lin MI, Huang Y, Yu J, Bauer PM, Giordano FJ, Sessa WC. Reexpression of caveolin-1 in endothelium rescues the vascular, cardiac, and pulmonary defects in global caveolin-1 knockout mice. J Exp Med 2007; 204(10): 2373–2382CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Razani B, Zhang XL, Bitzer M, von Gersdorff G, Böttinger EP, Lisanti MP. Caveolin-1 regulates transforming growth factor (TGF)- β/SMAD signaling through an interaction with the TGF-β type I receptor. J Biol Chem 2001; 276(9): 6727–6738CrossRefPubMedGoogle Scholar
  39. 39.
    Lee EK, Lee YS, Han IO, Park SH. Expression of Caveolin-1 reduces cellular responses to TGF-β1 through down-regulating the expression of TGF-β type II receptor gene in NIH3T3 fibroblast cells. Biochem Biophys Res Commun 2007; 359(2): 385–390CrossRefPubMedGoogle Scholar
  40. 40.
    Tourkina E, Gooz P, Pannu J, Bonner M, Scholz D, Hacker S, Silver RM, Trojanowska M, Hoffman S. Opposing effects of protein kinase Cα and protein kinase Cepsilon on collagen expression by human lung fibroblasts are mediated via MEK/ERK and caveolin-1 signaling. J Biol Chem 2005; 280(14): 13879–13887CrossRefPubMedGoogle Scholar
  41. 41.
    Royce SG, Le Saux CJ. Role of caveolin-1 in asthma and chronic inflammatory respiratory diseases. Expert Rev Respir Med 2014; 8(3): 339–347CrossRefPubMedGoogle Scholar
  42. 42.
    Cohen AW, Park DS, Woodman SE, Williams TM, Chandra M, Shirani J, Pereira de Souza A, Kitsis RN, Russell RG, Weiss LM, Tang B, Jelicks LA, Factor SM, Shtutin V, Tanowitz HB, Lisanti MP. Caveolin-1 null mice develop cardiac hypertrophy with hyperactivation of p42/44 MAP kinase in cardiac fibroblasts. Am J Physiol Cell Physiol 2003; 284(2): C457–C474CrossRefPubMedGoogle Scholar
  43. 43.
    Patel HH, Tsutsumi YM, Head BP, Niesman IR, Jennings M, Horikawa Y, Huang D, Moreno AL, Patel PM, Insel PA, Roth DM. Mechanisms of cardiac protection from ischemia/reperfusion injury: a role for caveolae and caveolin-1. FASEB J 2007; 21(7): 1565–1574CrossRefPubMedGoogle Scholar
  44. 44.
    Bach FC, Zhang Y, Miranda-Bedate A, Verdonschot LC, Bergknut N, Creemers LB, Ito K, Sakai D, Chan D, Meij BP, Tryfonidou MA. Increased caveolin-1 in intervertebral disc degeneration facilitates repair. Arthritis Res Ther 2015; 18(59): 59Google Scholar
  45. 45.
    Zhang C, Su X, Bellner L, Lin DH. Caveolin-1 regulates corneal wound healing by modulating Kir4.1 activity. Am J Physiol Cell Physiol 2016; 310(11): C993–C1000CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Scherer PE, Okamoto T, Chun M, Nishimoto I, Lodish HF, Lisanti MP. Identification, sequence, and expression of caveolin-2 defines a caveolin gene family. Proc Natl Acad Sci USA 1996; 93(1): 131–135CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Kwon H, Lee J, Jeong K, Jang D, Pak Y. A novel actin cytoskeletondependent noncaveolar microdomain composed of homo-oligomeric caveolin-2 for activation of insulin signaling. Biochim Biophys Acta 2013; 1833(10): 2176–2189CrossRefPubMedGoogle Scholar
  48. 48.
    Engelman JA, Zhang XL, Lisanti MP. Genes encoding human caveolin-1 and-2 are co-localized to the D7S522 locus (7q31.1), a known fragile site (FRA7G) that is frequently deleted in human cancers. FEBS Lett 1998; 436(3): 403–410CrossRefPubMedGoogle Scholar
  49. 49.
    Scherer PE, Lewis RY, Volonté D, Engelman JA, Galbiati F, Couet J, Kohtz DS, van Donselaar E, Peters P, Lisanti MP. Cell-type and tissue-specific expression of caveolin-2. Caveolins 1 and 2 colocalize and form a stable hetero-oligomeric complex in vivo. J Biol Chem 1997; 272(46): 29337–29346CrossRefPubMedGoogle Scholar
  50. 50.
    Razani B, Wang XB, Engelman JA, Battista M, Lagaud G, Zhang XL, Kneitz B, Hou H Jr, Christ GJ, Edelmann W, Lisanti MP. Caveolin-2-deficient mice show evidence of severe pulmonary dysfunction without disruption of caveolae. Mol Cell Biol 2002; 22(7): 2329–2344CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Frank PG, Woodman SE, Park DS, Lisanti MP. Caveolin, caveolae, and endothelial cell function. Arterioscler Thromb Vasc Biol 2003; 23(7): 1161–1168CrossRefPubMedGoogle Scholar
  52. 52.
    Lee S, Kwon H, Jeong K, Pak Y. Regulation of cancer cell proliferation by caveolin-2 down-regulation and re-expression. Int J Oncol 2011; 38(5): 1395–1402CrossRefPubMedGoogle Scholar
  53. 53.
    Shatseva T, Lee DY, Deng Z, Yang BB. MicroRNA miR-199a-3p regulates cell proliferation and survival by targeting caveolin-2. J Cell Sci 2011; 124(Pt 16): 2826–2836CrossRefPubMedGoogle Scholar
  54. 54.
    Yamasaki T, Seki N, Yoshino H, Itesako T, Hidaka H, Yamada Y, Tatarano S, Yonezawa T, Kinoshita T, Nakagawa M, Enokida H. MicroRNA-218 inhibits cell migration and invasion in renal cell carcinoma through targeting caveolin-2 involved in focal adhesion pathway. J Urol 2013; 190(3): 1059–1068CrossRefPubMedGoogle Scholar
  55. 55.
    Scherer PE, Okamoto T, Chun M, Nishimoto I, Lodish HF, Lisanti MP. Identification, sequence, and expression of caveolin-2 defines a caveolin gene family. Proc Natl Acad Sci USA 1996; 93(1): 131–135CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Sagara Y, Mimori K, Yoshinaga K, Tanaka F, Nishida K, Ohno S, Inoue H, Mori M. Clinical significance of caveolin-1, caveolin-2 and HER2/neu mRNA expression in human breast cancer. Br J Cancer 2004; 91(5): 959–965CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    López IP, Milagro FI, Martí A, Moreno-Aliaga MJ, Martínez JA, De Miguel C. Gene expression changes in rat white adipose tissue after a high-fat diet determined by differential display. Biochem Biophys Res Commun 2004; 318(1): 234–239CrossRefPubMedGoogle Scholar
  58. 58.
    Zaas DW, Duncan MJ, Li G, Wright JR, Abraham SN. Pseudomonas invasion of type I pneumocytes is dependent on the expression and phosphorylation of caveolin-2. J Biol Chem 2005; 280(6): 4864–4872CrossRefPubMedGoogle Scholar
  59. 59.
    Totta P, Gionfra F, Busonero C, Acconcia F. Modulation of 17β-estradiol signaling on cellular proliferation by caveolin-2. J Cell Physiol 2016; 231(6): 1219–1225CrossRefPubMedGoogle Scholar
  60. 60.
    Tang Z, Scherer PE, Okamoto T, Song K, Chu C, Kohtz DS, Nishimoto I, Lodish HF, Lisanti MP. Molecular cloning of caveolin- 3, a novel member of the caveolin gene family expressed predominantly in muscle. J Biol Chem 1996; 271(4): 2255–2261CrossRefPubMedGoogle Scholar
  61. 61.
    Hagiwara Y, Sasaoka T, Araishi K, Imamura M, Yorifuji H, Nonaka I, Ozawa E, Kikuchi T. Caveolin-3 deficiency causes muscle degeneration in mice. Hum Mol Genet. 2000;9(20):3047–3054CrossRefPubMedGoogle Scholar
  62. 62.
    Kim JH, Peng D, Schlebach JP, Hadziselimovic A, Sanders CR. Modest effects of lipid modifications on the structure of caveolin-3. Biochemistry 2014; 53(27): 4320–4322CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Schmitz M, Zerr I, Althaus HH. Effect of cavtratin, a caveolin-1 scaffolding domain peptide, on oligodendroglial signaling cascades. Cell Mol Neurobiol 2011; 31(7): 991–997CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Olmo-Turrubiarte AD, Calzada-Torres A, Díaz-Rosas G, Palma-Lara I, Sánchez-Urbina R, Garcia-Alonso P, Contreras-Ramos A. Mouse models for the study of postnatal cardiac hypertrophy. IJC Heart Vasculature 2015; 103: 131–140CrossRefGoogle Scholar
  65. 65.
    Markandeya YS, Phelan LJ, Woon MT, Keefe AM, Reynolds CR, August BK, Hacker TA, Roth DM, Patel HH, Balijepalli RC. Caveolin-3 overexpression attenuates cardiac hypertrophy via inhibition of T-type Ca2+ current modulated by protein kinase Cα in cardiomyocytes. J Biol Chem 2015; 290(36): 22085–22100CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Stoppani E, Rossi S, Meacci E, Penna F, Costelli P, Bellucci A, Faggi F, Maiolo D, Monti E, Fanzani A. Point mutated caveolin-3 form (P104L) impairs myoblast differentiation via Akt and p38 signalling reduction, leading to an immature cell signature. Biochim Biophys Acta 2011; 1812(4): 468–479CrossRefPubMedGoogle Scholar
  67. 67.
    Lei S, Li H, Xu J, Liu Y, Gao X, Wang J, Ng KFJ, Lau WB, Ma XL, Rodrigues B, Irwin MG, Xia Z. Hyperglycemia-induced protein kinase C β2 activation induces diastolic cardiac dysfunction in diabetic rats by impairing caveolin-3 expression and Akt/eNOS signaling. Diabetes 2013; 62(7): 2318–2328CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Tran C, Stary CM, Schilling JM, Bentley B, Patel HH, Roth DM. Role of caveolin-3 in lymphocyte activation. Life Sci 2015; 121: 35–39CrossRefPubMedGoogle Scholar
  69. 69.
    Zhao H, Zhang QR, Zhang HP, Chen XX. Effects of hyperbaric oxygen on the expression of caveolin-2 in brain tissues and the blood brain barrier after focal cerebral ischemia and reperfusion. Chin J Phys Med Rehabil (Zhonghua Wu Li Yi Xue Yu Kang Fu Za Zhi) 2011;33(9):652–655 (in Chinese)Google Scholar

Copyright information

© Higher Education Press and Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of PharmacyHarbin Medical UniversityHarbinChina

Personalised recommendations