1932

Abstract

The plasma membrane of eukaryotic cells is not a simple sheet of lipids and proteins but is differentiated into subdomains with crucial functions. Caveolae, small pits in the plasma membrane, are the most abundant surface subdomains of many mammalian cells. The cellular functions of caveolae have long remained obscure, but a new molecular understanding of caveola formation has led to insights into their workings. Caveolae are formed by the coordinated action of a number of lipid-interacting proteins to produce a microdomain with a specific structure and lipid composition. Caveolae can bud from the plasma membrane to form an endocytic vesicle or can flatten into the membrane to help cells withstand mechanical stress. The role of caveolae as mechanoprotective and signal transduction elements is reviewed in the context of disease conditions associated with caveola dysfunction.

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2018-10-06
2024-06-14
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Literature Cited

  1. Aboulaich N, Chui PC, Asara JM, Flier JS, Maratos-Flier E 2011. Polymerase I and transcript release factor regulates lipolysis via a phosphorylation-dependent mechanism. Diabetes 60:757–65
    [Google Scholar]
  2. Andreone BJ, Chow BW, Tata A, Lacoste B, Ben-Zvi A et al. 2017. Blood-brain barrier permeability is regulated by lipid transport–dependent suppression of caveolae-mediated transcytosis. Neuron 94:581–94.e5
    [Google Scholar]
  3. Ariotti N, Fernandez-Rojo MA, Zhou Y, Hill MM, Rodkey TL et al. 2014. Caveolae regulate the nanoscale organization of the plasma membrane to remotely control Ras signaling. J. Cell Biol. 204:777–92
    [Google Scholar]
  4. Ariotti N, Hall TE, Rae J, Ferguson C, McMahon KA et al. 2015.a Modular detection of GFP-labeled proteins for rapid screening by electron microscopy in cells and organisms. Dev. Cell 35:513–25
    [Google Scholar]
  5. Ariotti N, Rae J, Leneva N, Ferguson C, Loo D et al. 2015.b Molecular characterization of caveolin-induced membrane curvature. J. Biol. Chem. 290:24875–90
    [Google Scholar]
  6. Asterholm IW, Mundy DI, Weng J, Anderson RG, Scherer PE 2012. Altered mitochondrial function and metabolic inflexibility associated with loss of caveolin-1. Cell Metab 15:171–85
    [Google Scholar]
  7. Astudillo AM, Perez-Chacon G, Meana C, Balgoma D, Pol A et al. 2011. Altered arachidonate distribution in macrophages from caveolin-1 null mice leading to reduced eicosanoid synthesis. J. Biol. Chem. 286:35299–307
    [Google Scholar]
  8. Bai L, Deng X, Li J, Wang M, Li Q et al. 2011. Regulation of cellular senescence by the essential caveolar component PTRF/Cavin-1. Cell Res 21:1088–101
    [Google Scholar]
  9. Bastiani M, Liu L, Hill MM, Jedrychowski MP, Nixon SJ et al. 2009. MURC/Cavin-4 and cavin family members form tissue-specific caveolar complexes. J. Cell Biol. 185:1259–73
    [Google Scholar]
  10. Boettcher JP, Kirchner M, Churin Y, Kaushansky A, Pompaiah M et al. 2010. Tyrosine-phosphorylated caveolin-1 blocks bacterial uptake by inducing Vav2-RhoA-mediated cytoskeletal rearrangements. PLOS Biol 8:e1000457
    [Google Scholar]
  11. Boopathy GTK, Kulkarni M, Ho SY, Boey A, Chua EWM et al. 2017. Cavin-2 regulates the activity and stability of endothelial nitric-oxide synthase (eNOS) in angiogenesis. J. Biol. Chem. 292:17760–76
    [Google Scholar]
  12. Borcherding N, Kusner D, Liu GH, Zhang W 2014. ROR1, an embryonic protein with an emerging role in cancer biology. Protein Cell 5:496–502
    [Google Scholar]
  13. Bosch M, Mari M, Herms A, Fernandez A, Fajardo A et al. 2011. Caveolin-1 deficiency causes cholesterol-dependent mitochondrial dysfunction and apoptotic susceptibility. Curr. Biol. 21:681–86
    [Google Scholar]
  14. Boucrot E, Howes MT, Kirchhausen T, Parton RG 2011. Redistribution of caveolae during mitosis. J. Cell Sci. 124:1965–72
    [Google Scholar]
  15. Breen MR, Camps M, Carvalho-Simoes F, Zorzano A, Pilch PF 2012. Cholesterol depletion in adipocytes causes caveolae collapse concomitant with proteosomal degradation of cavin-2 in a switch-like fashion. PLOS ONE 7:e34516
    [Google Scholar]
  16. Bucci M, Gratton JP, Rudic RD, Acevedo L, Roviezzo F et al. 2000. In vivo delivery of the caveolin-1 scaffolding domain inhibits nitric oxide synthesis and reduces inflammation. Nat. Med. 6:1362–67
    [Google Scholar]
  17. Byrne DP, Dart C, Rigden DJ 2012. Evaluating caveolin interactions: Do proteins interact with the caveolin scaffolding domain through a widespread aromatic residue-rich motif. ? PLOS ONE 7:e44879
    [Google Scholar]
  18. Cai C, Weisleder N, Ko JK, Komazaki S, Sunada Y et al. 2009. Membrane repair defects in muscular dystrophy are linked to altered interaction between MG53, caveolin-3, and dysferlin. J. Biol. Chem. 284:15894–902
    [Google Scholar]
  19. Cao H, Alston L, Ruschman J, Hegele RA 2008. Heterozygous CAV1 frameshift mutations (MIM 601047) in patients with atypical partial lipodystrophy and hypertriglyceridemia. Lipids Health Dis 7:3
    [Google Scholar]
  20. Cao H, Courchesne WE, Mastick CC 2002. A phosphotyrosine-dependent protein interaction screen reveals a role for phosphorylation of caveolin-1 on tyrosine 14: recruitment of C-terminal Src kinase. J. Biol. Chem. 277:8771–74
    [Google Scholar]
  21. Cao H, Sanguinetti AR, Mastick CC 2004. Oxidative stress activates both Src-kinases and their negative regulator Csk and induces phosphorylation of two targeting proteins for Csk: caveolin-1 and paxillin. Exp. Cell Res. 294:159–71
    [Google Scholar]
  22. Cerezo A, Guadamillas MC, Goetz JG, Sanchez-Perales S, Klein E et al. 2009. The absence of caveolin-1 increases proliferation and anchorage- independent growth by a Rac-dependent, Erk-independent mechanism. Mol. Cell. Biol. 29:5046–59
    [Google Scholar]
  23. Chaudhary N, Gomez GA, Howes MT, Lo HP, McMahon KA et al. 2014. Endocytic crosstalk: Cavins, caveolins, and caveolae regulate clathrin-independent endocytosis. PLOS Biol 12:e1001832
    [Google Scholar]
  24. Cheng JP, Mendoza-Topaz C, Howard G, Chadwick J, Shvets E et al. 2015. Caveolae protect endothelial cells from membrane rupture during increased cardiac output. J. Cell Biol. 211:53–61
    [Google Scholar]
  25. Collins BM, Davis MJ, Hancock JF, Parton RG 2012. Structure-based reassessment of the caveolin signaling model: Do caveolae regulate signaling through caveolin-protein interactions. ? Dev. Cell 23:11–20
    [Google Scholar]
  26. Copeland CA, Han B, Tiwari A, Austin ED, Loyd JE et al. 2017. A disease-associated frameshift mutation in caveolin-1 disrupts caveolae formation and function through introduction of a de novo ER retention signal. Mol. Biol. Cell 28:3095–111
    [Google Scholar]
  27. Corrotte M, Almeida PE, Tam C, Castro-Gomes T, Fernandes MC et al. 2013. Caveolae internalization repairs wounded cells and muscle fibers. eLife 2:e00926
    [Google Scholar]
  28. Couet J, Li S, Okamoto T, Ikezu T, Lisanti MP 1997. Identification of peptide and protein ligands for the caveolin-scaffolding domain. Implications for the interaction of caveolin with caveolae-associated proteins. J. Biol. Chem. 272:6525–33
    [Google Scholar]
  29. Damm EM, Pelkmans L, Kartenbeck J, Mezzacasa A, Kurzchalia T, Helenius A 2005. Clathrin- and caveolin-1-independent endocytosis: entry of simian virus 40 into cells devoid of caveolae. J. Cell Biol. 168:477–88
    [Google Scholar]
  30. del Pozo MA, Balasubramanian N, Alderson NB, Kiosses WB, Grande-Garcia A et al. 2005. Phospho-caveolin-1 mediates integrin-regulated membrane domain internalization. Nat. Cell Biol. 7:901–8
    [Google Scholar]
  31. Dietzen DJ, Hastings WR, Lublin DM 1995. Caveolin is palmitoylated on multiple cysteine residues. Palmitoylation is not necessary for localization of caveolin to caveolae. J. Biol. Chem. 270:6838–42
    [Google Scholar]
  32. Drab M, Verkade P, Elger M, Kasper M, Lohn M et al. 2001. Loss of caveolae, vascular dysfunction, and pulmonary defects in caveolin-1 gene–disrupted mice. Science 9:9
    [Google Scholar]
  33. Dulhunty AF, Franzini-Armstrong C 1975. The relative contributions of the folds and caveolae to the surface membrane of frog skeletal muscle fibres at different sarcomere lengths. J. Physiol. 250:513–39
    [Google Scholar]
  34. Echarri A, Del Pozo MA 2015. Caveolae: mechanosensitive membrane invaginations linked to actin filaments. J. Cell Sci. 128:2747–58
    [Google Scholar]
  35. Elliott MH, Ashpole NE, Gu X, Herrnberger L, McClellan ME et al. 2016. Caveolin-1 modulates intraocular pressure: implications for caveolae mechanoprotection in glaucoma. Sci. Rep. 6:37127
    [Google Scholar]
  36. Fernandez MA, Albor C, Ingelmo-Torres M, Nixon SJ, Ferguson C et al. 2006. Caveolin-1 is essential for liver regeneration. Science 313:1628–32
    [Google Scholar]
  37. Fernandez-Rojo MA, Gongora M, Fitzsimmons RL, Martel N, Martin SD et al. 2013. Caveolin-1 is necessary for hepatic oxidative lipid metabolism: evidence for crosstalk between caveolin-1 and bile acid signaling. Cell Rep 4:238–47
    [Google Scholar]
  38. Fra AM, Williamson E, Simons K, Parton RG 1994. Detergent-insoluble glycolipid microdomains in lymphocytes in the absence of caveolae. J. Biol. Chem. 269:30745–48
    [Google Scholar]
  39. Frank PG, Cheung MW, Pavlides S, Llaverias G, Park DS, Lisanti MP 2006. Caveolin-1 and regulation of cellular cholesterol homeostasis. Am. J. Physiol. Heart Circ. Physiol. 291:H677–86
    [Google Scholar]
  40. Fridolfsson HN, Kawaraguchi Y, Ali SS, Panneerselvam M, Niesman IR et al. 2012. Mitochondria-localized caveolin in adaptation to cellular stress and injury. FASEB J 26:4637–49
    [Google Scholar]
  41. Galbiati F, Volonte D, Minetti C, Bregman DB, Lisanti MP 2000. Limb-girdle muscular dystrophy (LGMD-1C) mutants of caveolin-3 undergo ubiquitination and proteasomal degradation: Treatment with proteasomal inhibitors blocks the dominant negative effect of LGMD-1C mutants and rescues wild-type caveolin-3. J. Biol. Chem. 275:37702–11
    [Google Scholar]
  42. Galbiati F, Volonte D, Minetti C, Chu JB, Lisanti MP 1999. Phenotypic behavior of caveolin-3 mutations that cause autosomal dominant limb girdle muscular dystrophy (LGMD-1C). Retention of LGMD-1C caveolin-3 mutants within the Golgi complex. J. Biol. Chem. 274:25632–41
    [Google Scholar]
  43. Gambin Y, Ariotti N, McMahon KA, Bastiani M, Sierecki E et al. 2014. Single-molecule analysis reveals self assembly and nanoscale segregation of two distinct cavin subcomplexes on caveolae. eLife 3:e01434
    [Google Scholar]
  44. Garcia-Cardena G, Martasek P, Masters BS, Skidd PM, Couet J et al. 1997. Dissecting the interaction between nitric oxide synthase (NOS) and caveolin. Functional significance of the NOS caveolin binding domain in vivo. J. Biol. Chem. 272:25437–40
    [Google Scholar]
  45. Garg A, Agarwal AK 2008. Caveolin-1: a new locus for human lipodystrophy. J. Clin. Endocrinol. Metab. 93:1183–85
    [Google Scholar]
  46. Gaus K, Le Lay S, Balasubramanian N, Schwartz MA 2006. Integrin-mediated adhesion regulates membrane order. J. Cell Biol. 174:725–34
    [Google Scholar]
  47. Gratton JP, Lin MI, Yu J, Weiss ED, Jiang ZL et al. 2003. Selective inhibition of tumor microvascular permeability by cavtratin blocks tumor progression in mice. Cancer Cell 4:31–39
    [Google Scholar]
  48. Hailstones D, Sleer LS, Parton RG, Stanley KK 1998. Regulation of caveolin and caveolae by cholesterol in MDCK cells. J. Lipid Res. 39:369–79
    [Google Scholar]
  49. Han B, Copeland CA, Kawano Y, Rosenzweig EB, Austin ED et al. 2016. Characterization of a caveolin-1 mutation associated with both pulmonary arterial hypertension and congenital generalized lipodystrophy. Traffic 17:1297–312
    [Google Scholar]
  50. Hansen CG, Bright NA, Howard G, Nichols BJ 2009. SDPR induces membrane curvature and functions in the formation of caveolae. Nat. Cell Biol. 11:807–14
    [Google Scholar]
  51. Hansen CG, Howard G, Nichols BJ 2011. Pacsin 2 is recruited to caveolae and functions in caveolar biogenesis. J. Cell Sci. 124:2777–85
    [Google Scholar]
  52. Hansen CG, Shvets E, Howard G, Riento K, Nichols BJ 2013. Deletion of cavin genes reveals tissue-specific mechanisms for morphogenesis of endothelial caveolae. Nat. Commun. 4:1831
    [Google Scholar]
  53. Hayashi YK, Matsuda C, Ogawa M, Goto K, Tominaga K et al. 2009. Human PTRF mutations cause secondary deficiency of caveolins resulting in muscular dystrophy with generalized lipodystrophy. J. Clin. Investig. 119:2623–33
    [Google Scholar]
  54. Hayer A, Stoeber M, Bissig C, Helenius A 2010.a Biogenesis of caveolae: stepwise assembly of large caveolin and cavin complexes. Traffic 11:361–82
    [Google Scholar]
  55. Hayer A, Stoeber M, Ritz D, Engel S, Meyer HH, Helenius A 2010.b Caveolin-1 is ubiquitinated and targeted to intralumenal vesicles in endolysosomes for degradation. J. Cell Biol. 191:615–29
    [Google Scholar]
  56. Head BP, Peart JN, Panneerselvam M, Yokoyama T, Pearn ML et al. 2010. Loss of caveolin-1 accelerates neurodegeneration and aging. PLOS ONE 5:e15697
    [Google Scholar]
  57. Henley JR, Krueger EW, Oswald BJ, McNiven MA 1998. Dynamin-mediated internalization of caveolae. J. Cell Biol. 141:85–99
    [Google Scholar]
  58. Hernandez VJ, Weng J, Ly P, Pompey S, Dong H et al. 2013. Cavin-3 dictates the balance between ERK and Akt signaling. eLife 2:e00905
    [Google Scholar]
  59. Hernandez-Deviez DJ, Martin S, Laval SH, Lo HP, Cooper ST et al. 2006. Aberrant dysferlin trafficking in cells lacking caveolin or expressing dystrophy mutants of caveolin-3. Hum. Mol. Genet. 15:129–42
    [Google Scholar]
  60. Hertzog M, Monteiro P, Le Dez G, Chavrier P 2012. Exo70 subunit of the exocyst complex is involved in adhesion-dependent trafficking of caveolin-1. PLOS ONE 7:e52627
    [Google Scholar]
  61. Hill MM, Bastiani M, Luetterforst R, Kirkham M, Kirkham A et al. 2008. PTRF-Cavin, a conserved cytoplasmic protein required for caveola formation and function. Cell 132:113–24
    [Google Scholar]
  62. Hirama T, Das R, Yang Y, Ferguson C, Won A et al. 2017. Phosphatidylserine dictates the assembly and dynamics of caveolae in the plasma membrane. J. Biol. Chem. 292:14292–307
    [Google Scholar]
  63. Hoffmann C, Berking A, Agerer F, Buntru A, Neske F et al. 2010. Caveolin limits membrane microdomain mobility and integrin-mediated uptake of fibronectin-binding pathogens. J. Cell Sci. 123:4280–91
    [Google Scholar]
  64. Ikonen E, Parton RG 2000. Caveolins and cellular cholesterol balance. Traffic 1:212–17
    [Google Scholar]
  65. Isshiki M, Ando J, Korenaga R, Kogo H, Fujimoto T et al. 1998. Endothelial Ca2+ waves preferentially originate at specific loci in caveolin-rich cell edges. PNAS 95:5009–14
    [Google Scholar]
  66. Jansa P, Burek C, Sander EE, Grummt I 2001. The transcript release factor PTRF augments ribosomal gene transcription by facilitating reinitiation of RNA polymerase I. Nucleic Acids Res 29:423–29
    [Google Scholar]
  67. Jansa P, Mason SW, Hoffmann-Rohrer U, Grummt I 1998. Cloning and functional characterization of PTRF, a novel protein which induces dissociation of paused ternary transcription complexes. EMBO J 17:2855–64
    [Google Scholar]
  68. Joshi B, Bastiani M, Strugnell SS, Boscher C, Parton RG, Nabi IR 2012. Phosphocaveolin-1 is a mechanotransducer that induces caveola biogenesis via Egr1 transcriptional regulation. J. Cell Biol. 199:425–35
    [Google Scholar]
  69. Joshi B, Strugnell SS, Goetz JG, Kojic LD, Cox ME et al. 2008. Phosphorylated caveolin-1 regulates Rho/ROCK-dependent focal adhesion dynamics and tumor cell migration and invasion. Cancer Res 68:8210–20
    [Google Scholar]
  70. Jung W, Sierecki E, Bastiani M, O'Carroll A, Alexandrov K et al. 2018. Cell-free formation and interactome analysis of caveolae. J. Cell Biol. 217:2141–65
    [Google Scholar]
  71. Khan T, Muise ES, Iyengar P, Wang ZV, Chandalia M et al. 2009. Metabolic dysregulation and adipose tissue fibrosis: role of collagen VI. Mol. Cell. Biol. 29:1575–91
    [Google Scholar]
  72. Kim CA, Delepine M, Boutet E, El Mourabit H, Le Lay S et al. 2008. Association of a homozygous nonsense caveolin-1 mutation with Berardinelli-Seip congenital lipodystrophy. J. Clin. Endocrinol. Metab. 93:1129–34
    [Google Scholar]
  73. Kirkham M, Fujita A, Chadda R, Nixon SJ, Kurzchalia TV et al. 2005. Ultrastructural identification of uncoated caveolin-independent early endocytic vehicles. J. Cell Biol. 168:465–76
    [Google Scholar]
  74. Kirkham M, Nixon SJ, Howes MT, Abi-Rached L, Wakeham DE et al. 2008. Evolutionary analysis and molecular dissection of caveola biogenesis. J. Cell Sci. 121:2075–86
    [Google Scholar]
  75. Koleske AJ, Baltimore D, Lisanti MP 1995. Reduction of caveolin and caveolae in oncogenically transformed cells. PNAS 92:1381–85
    [Google Scholar]
  76. Kovtun O, Tillu VA, Ariotti N, Parton RG, Collins BM 2015. Cavin family proteins and the assembly of caveolae. J. Cell Sci. 128:1269–78
    [Google Scholar]
  77. Kovtun O, Tillu VA, Jung W, Leneva N, Ariotti N et al. 2014. Structural insights into the organization of the cavin membrane coat complex. Dev. Cell 31:405–19
    [Google Scholar]
  78. Lahtinen U, Honsho M, Parton RG, Simons K, Verkade P 2003. Involvement of caveolin-2 in caveolar biogenesis in MDCK cells. FEBS Lett 538:85–88
    [Google Scholar]
  79. Le Lay S, Hajduch E, Lindsay MR, Le Liepvre X, Thiele C et al. 2006. Cholesterol-induced caveolin targeting to lipid droplets in adipocytes: a role for caveolar endocytosis. Traffic 7:549–61
    [Google Scholar]
  80. Lee CY, Lai TY, Tsai MK, Chang YC, Ho YH et al. 2017. The ubiquitin ligase ZNRF1 promotes caveolin-1 ubiquitination and degradation to modulate inflammation. Nat. Commun. 8:15502
    [Google Scholar]
  81. Lee J, Schmid-Schonbein GW 1995. Biomechanics of skeletal muscle capillaries: hemodynamic resistance, endothelial distensibility, and pseudopod formation. Ann. Biomed. Eng. 23:226–46
    [Google Scholar]
  82. Lee SW, Reimer CL, Oh P, Campbell DB, Schnitzer JE 1998. Tumor cell growth inhibition by caveolin re-expression in human breast cancer cells. Oncogene 16:1391–97
    [Google Scholar]
  83. Lim JY, Barnett TC, Bastiani M, McMahon KA, Ferguson C et al. 2017. Caveolin-1 restricts group A Streptococcus invasion of non-phagocytic host cells. Cell. Microbiol. 19:e12772
    [Google Scholar]
  84. Lim YW, Lo HP, Ferguson C, Martel N, Giacomotto J et al. 2017. Caveolae protect notochord cells against catastrophic mechanical failure during development. Curr. Biol. 27:1968–81.e7
    [Google Scholar]
  85. Liu L, Brown D, McKee M, Lebrasseur NK, Yang D et al. 2008. Deletion of Cavin/PTRF causes global loss of caveolae, dyslipidemia, and glucose intolerance. Cell Metab 8:310–17
    [Google Scholar]
  86. Liu L, Hansen CG, Honeyman BJ, Nichols BJ, Pilch PF 2014. Cavin-3 knockout mice show that cavin-3 is not essential for caveolae formation, for maintenance of body composition, or for glucose tolerance. PLOS ONE 9:e102935
    [Google Scholar]
  87. Liu L, Pilch PF 2016. PTRF/Cavin-1 promotes efficient ribosomal RNA transcription in response to metabolic challenges. eLife 5:e17508
    [Google Scholar]
  88. Lo HP, Nixon SJ, Hall TE, Cowling BS, Ferguson C et al. 2015. The caveolin-cavin system plays a conserved and critical role in mechanoprotection of skeletal muscle. J. Cell Biol. 210:833–49
    [Google Scholar]
  89. Ludwig A, Nichols BJ, Sandin S 2016. Architecture of the caveolar coat complex. J. Cell Sci. 129:3077–83
    [Google Scholar]
  90. Marsboom G, Chen Z, Yuan Y, Zhang Y, Tiruppathi C et al. 2017. Aberrant caveolin-1-mediated Smad signaling and proliferation identified by analysis of adenine 474 deletion mutation (c.474delA) in patient fibroblasts: a new perspective on the mechanism of pulmonary hypertension. Mol. Biol. Cell 28:1177–85
    [Google Scholar]
  91. Martin S, Fernandez-Rojo MA, Stanley AC, Bastiani M, Okano S et al. 2012. Caveolin-1 deficiency leads to increased susceptibility to cell death and fibrosis in white adipose tissue: characterization of a lipodystrophic model. PLOS ONE 7:e46242
    [Google Scholar]
  92. Matsuda C, Hayashi YK, Ogawa M, Aoki M, Murayama K et al. 2001. The sarcolemmal proteins dysferlin and caveolin-3 interact in skeletal muscle. Hum. Mol. Genet. 10:1761–66
    [Google Scholar]
  93. Mayor S, Parton RG, Donaldson JG 2014. Clathrin-independent pathways of endocytosis. Cold Spring Harb. Perspect. Biol. 6:a016758
    [Google Scholar]
  94. McMahon KA, Zajicek H, Li WP, Peyton MJ, Minna JD et al. 2009. SRBC/cavin-3 is a caveolin adapter protein that regulates caveolae function. EMBO J 28:1001–15
    [Google Scholar]
  95. McNally EM, de Sa Moreira E, Duggan DJ, Bonnemann CG, Lisanti MP et al. 1998. Caveolin-3 in muscular dystrophy. Hum. Mol. Genet. 7:871–77
    [Google Scholar]
  96. Meshulam T, Breen MR, Liu L, Parton RG, Pilch PF 2011. Caveolins/caveolae protect adipocytes from fatty acid–mediated lipotoxicity. J. Lipid Res. 52:1526–32
    [Google Scholar]
  97. Meshulam T, Simard JR, Wharton J, Hamilton JA, Pilch PF 2006. Role of caveolin-1 and cholesterol in transmembrane fatty acid movement. Biochemistry 45:2882–93
    [Google Scholar]
  98. Minetti C, Bado M, Broda P, Sotgia F, Bruno C et al. 2002. Impairment of caveolae formation and T-system disorganization in human muscular dystrophy with caveolin-3 deficiency. Am. J. Pathol. 160:265–70
    [Google Scholar]
  99. Minetti C, Sotgia F, Bruno C, Scartezzini P, Broda P et al. 1998. Mutations in the caveolin-3 gene cause autosomal dominant limb-girdle muscular dystrophy. Nat. Genet. 18:365–68
    [Google Scholar]
  100. Mohan J, Moren B, Larsson E, Holst MR, Lundmark R 2015. Cavin3 interacts with cavin1 and caveolin1 to increase surface dynamics of caveolae. J. Cell Sci. 128:979–91
    [Google Scholar]
  101. Monier S, Parton RG, Vogel F, Behlke J, Henske A, Kurzchalia TV 1995. VIP21-caveolin, a membrane protein constituent of the caveolar coat, oligomerizes in vivo and in vitro. Mol. Biol. Cell 6:911–27
    [Google Scholar]
  102. Moon H, Lee CS, Inder KL, Sharma S, Choi E et al. 2014. PTRF/cavin-1 neutralizes non-caveolar caveolin-1 microdomains in prostate cancer. Oncogene 33:3561–70
    [Google Scholar]
  103. Moren B, Shah C, Howes MT, Schieber NL, McMahon HT et al. 2012. EHD2 regulates caveolar dynamics via ATP-driven targeting and oligomerization. Mol. Biol. Cell 23:1316–29
    [Google Scholar]
  104. Murata M, Peranen J, Schreiner R, Wieland F, Kurzchalia TV, Simons K 1995. VIP21/caveolin is a cholesterol-binding protein. PNAS 92:10339–43
    [Google Scholar]
  105. Oh P, Borgstrom P, Witkiewicz H, Li Y, Borgstrom BJ et al. 2007. Live dynamic imaging of caveolae pumping targeted antibody rapidly and specifically across endothelium in the lung. Nat. Biotechnol. 25:327–37
    [Google Scholar]
  106. Oh P, McIntosh DP, Schnitzer JE 1998. Dynamin at the neck of caveolae mediates their budding to form transport vesicles by GTP-driven fission from the plasma membrane of endothelium. J. Cell Biol. 141:101–14
    [Google Scholar]
  107. Okamoto T, Schlegel A, Scherer PE, Lisanti MP 1998. Caveolins, a family of scaffolding proteins for organizing “preassembled signaling complexes” at the plasma membrane. J. Biol. Chem. 273:5419–22
    [Google Scholar]
  108. Orlichenko L, Huang B, Krueger E, McNiven MA 2006. Epithelial growth factor–induced phosphorylation of caveolin 1 at tyrosine 14 stimulates caveolae formation in epithelial cells. J. Biol. Chem. 281:4570–79
    [Google Scholar]
  109. Ortegren U, Karlsson M, Blazic N, Blomqvist M, Nystrom FH et al. 2004. Lipids and glycosphingolipids in caveolae and surrounding plasma membrane of primary rat adipocytes. Eur. J. Biochem. 271:2028–36
    [Google Scholar]
  110. Ozturk S, Papageorgis P, Wong CK, Lambert AW, Abdolmaleky HM et al. 2016. SDPR functions as a metastasis suppressor in breast cancer by promoting apoptosis. PNAS 113:638–43
    [Google Scholar]
  111. Palade GE, Bruns RR 1968. Structural modulations of plasmalemmal vesicles. J. Cell Biol. 37:633–49
    [Google Scholar]
  112. Park H, Go YM, Darji R, Choi JW, Lisanti MP et al. 2000. Caveolin-1 regulates shear stress–dependent activation of extracellular signal-regulated kinase. Am. J. Physiol. Heart Circ. Physiol. 278:H1285–93
    [Google Scholar]
  113. Parker S, Peterkin HS, Baylis HA 2007. Muscular dystrophy associated mutations in caveolin-1 induce neurotransmission and locomotion defects in Caenorhabditis elegans. Invertebr. . Neurosci 7:157–64
    [Google Scholar]
  114. Parker S, Walker DS, Ly S, Baylis HA 2009. Caveolin-2 is required for apical lipid trafficking and suppresses basolateral recycling defects in the intestine of Caenorhabditis elegans. Mol. Biol. . Cell 20:1763–71
    [Google Scholar]
  115. Parton RG, del Pozo MA 2013. Caveolae as plasma membrane sensors, protectors and organizers. Nat. Rev. Mol. Cell Biol. 14:98–112
    [Google Scholar]
  116. Parton RG, Joggerst B, Simons K 1994. Regulated internalization of caveolae. J. Cell Biol. 127:1199–215
    [Google Scholar]
  117. Parton RG, Tillu VA, Collins BM 2018. Caveolae. Curr Biol 28:R402–5
    [Google Scholar]
  118. Pelkmans L, Burli T, Zerial M, Helenius A 2004. Caveolin-stabilized membrane domains as multifunctional transport and sorting devices in endocytic membrane traffic. Cell 118:767–80
    [Google Scholar]
  119. Pol A, Martin S, Fernandez MA, Ferguson C, Carozzi A et al. 2004. Dynamic and regulated association of caveolin with lipid bodies: modulation of lipid body motility and function by a dominant negative mutant. Mol. Biol. Cell 15:99–110
    [Google Scholar]
  120. Pol A, Martin S, Fernandez MA, Ingelmo-Torres M, Ferguson C et al. 2005. Cholesterol and fatty acids regulate dynamic caveolin trafficking through the Golgi complex and between the cell surface and lipid bodies. Mol. Biol. Cell 16:2091–105
    [Google Scholar]
  121. Prinetti A, Aureli M, Illuzzi G, Prioni S, Nocco V et al. 2010. GM3 synthase overexpression results in reduced cell motility and in caveolin-1 upregulation in human ovarian carcinoma cells. Glycobiology 20:62–77
    [Google Scholar]
  122. Radel C, Rizzo V 2005. Integrin mechanotransduction stimulates caveolin-1 phosphorylation and recruitment of Csk to mediate actin reorganization. Am. J. Physiol. Heart Circ. Physiol. 288:H936–45
    [Google Scholar]
  123. Rajab A, Straub V, McCann LJ, Seelow D, Varon R et al. 2010. Fatal cardiac arrhythmia and long-QT syndrome in a new form of congenital generalized lipodystrophy with muscle rippling (CGL4) due to PTRF-CAVIN mutations. PLOS Genet 6:e1000874
    [Google Scholar]
  124. Razani B, Combs TP, Wang XB, Frank PG, Park DS et al. 2002.a Caveolin-1-deficient mice are lean, resistant to diet-induced obesity, and show hypertriglyceridemia with adipocyte abnormalities. J. Biol. Chem. 277:8635–47
    [Google Scholar]
  125. Razani B, Wang XB, Engelman JA, Battista M, Lagaud G et al. 2002.b Caveolin-2-deficient mice show evidence of severe pulmonary dysfunction without disruption of caveolae. Mol. Cell. Biol. 22:2329–44
    [Google Scholar]
  126. Repetto S, Bado M, Broda P, Lucania G, Masetti E et al. 1999. Increased number of caveolae and caveolin-3 overexpression in Duchenne muscular dystrophy. Biochem. Biophys. Res. Commun. 261:547–50
    [Google Scholar]
  127. Rippe B, Rosengren BI, Carlsson O, Venturoli D 2002. Transendothelial transport: the vesicle controversy. J. Vasc. Res. 39:375–90
    [Google Scholar]
  128. Ritz D, Vuk M, Kirchner P, Bug M, Schutz S et al. 2011. Endolysosomal sorting of ubiquitylated caveolin-1 is regulated by VCP and UBXD1 and impaired by VCP disease mutations. Nat. Cell Biol. 13:1116–23
    [Google Scholar]
  129. Rodriguez G, Ueyama T, Ogata T, Czernuszewicz G, Tan Y et al. 2011. Molecular genetic and functional characterization implicate muscle-restricted coiled-coil gene (MURC) as a causal gene for familial dilated cardiomyopathy. Circ. Cardiovasc. Genet. 4:349–58
    [Google Scholar]
  130. Rosengren BI, Rippe A, Rippe C, Venturoli D, Sward K, Rippe B 2006. Transvascular protein transport in mice lacking endothelial caveolae. Am. J. Physiol. Heart Circ. Physiol. 291:H1371–77
    [Google Scholar]
  131. Rothberg KG, Heuser JE, Donzell WC, Ying YS, Glenney JR, Anderson RG 1992. Caveolin, a protein component of caveolae membrane coats. Cell 68:673–82
    [Google Scholar]
  132. Sargiacomo M, Sudol M, Tang Z, Lisanti MP 1993. Signal transducing molecules and glycosyl-phosphatidylinositol-linked proteins form a caveolin-rich insoluble complex in MDCK cells. J. Cell Biol. 122:789–807
    [Google Scholar]
  133. Sato K, Sato M, Audhya A, Oegema K, Schweinsberg P, Grant BD 2006. Dynamic regulation of caveolin-1 trafficking in the germ line and embryo of Caenorhabditis elegans. Mol. Biol. . Cell 17:3085–94
    [Google Scholar]
  134. Scheel J, Srinivasan J, Honnert U, Henske A, Kurzchalia TV 1999. Involvement of caveolin-1 in meiotic cell-cycle progression in Caenorhabditis elegans. Nat. . Cell Biol 1:127–29
    [Google Scholar]
  135. Scherer PE, Lewis RY, Volonte D, Engelman JA, Galbiati F et al. 1997. Cell-type and tissue-specific expression of caveolin-2. Caveolins 1 and 2 co-localize and form a stable hetero-oligomeric complex in vivo. J. Biol. Chem. 272:29337–46
    [Google Scholar]
  136. Schubert W, Frank PG, Woodman SE, Hyogo H, Cohen DE et al. 2002. Microvascular hyperpermeability in caveolin-1 (−/−) knock-out mice. Treatment with a specific nitric-oxide synthase inhibitor, l-NAME, restores normal microvascular permeability in Cav-1 null mice. J. Biol. Chem. 277:40091–98
    [Google Scholar]
  137. Schubert W, Sotgia F, Cohen AW, Capozza F, Bonuccelli G et al. 2007. Caveolin-1(−/−)- and caveolin-2(−/−)-deficient mice both display numerous skeletal muscle abnormalities, with tubular aggregate formation. Am. J. Pathol. 170:316–33
    [Google Scholar]
  138. Seemann E, Sun M, Krueger S, Troger J, Hou W et al. 2017. Deciphering caveolar functions by syndapin III KO-mediated impairment of caveolar invagination. eLife 6:e29854
    [Google Scholar]
  139. Senju Y, Itoh Y, Takano K, Hamada S, Suetsugu S 2011. Essential role of PACSIN2/syndapin-II in caveolae membrane sculpting. J. Cell Sci. 124:2032–40
    [Google Scholar]
  140. Sharma DK, Brown JC, Choudhury A, Peterson TE, Holicky E et al. 2004. Selective stimulation of caveolar endocytosis by glycosphingolipids and cholesterol. Mol. Biol. Cell 15:3114–22
    [Google Scholar]
  141. Shastry S, Delgado MR, Dirik E, Turkmen M, Agarwal AK, Garg A 2010. Congenital generalized lipodystrophy, type 4 (CGL4) associated with myopathy due to novel PTRF mutations. Am. J. Med. Genet. A 152:2245–53
    [Google Scholar]
  142. Shvets E, Bitsikas V, Howard G, Hansen CG, Nichols BJ 2015. Dynamic caveolae exclude bulk membrane proteins and are required for sorting of excess glycosphingolipids. Nat. Commun. 6:6867
    [Google Scholar]
  143. Simard JR, Meshulam T, Pillai BK, Kirber MT, Brunaldi K et al. 2010. Caveolins sequester FA on the cytoplasmic leaflet of the plasma membrane, augment triglyceride formation, and protect cells from lipotoxicity. J. Lipid Res. 51:914–22
    [Google Scholar]
  144. Singh RD, Marks DL, Holicky EL, Wheatley CL, Kaptzan T et al. 2010. Gangliosides and β1-integrin are required for caveolae and membrane domains. Traffic 11:348–60
    [Google Scholar]
  145. Singh RD, Puri V, Valiyaveettil JT, Marks DL, Bittman R, Pagano RE 2003. Selective caveolin-1-dependent endocytosis of glycosphingolipids. Mol. Biol. Cell 14:3254–65
    [Google Scholar]
  146. Sinha B, Koster D, Ruez R, Gonnord P, Bastiani M et al. 2011. Cells respond to mechanical stress by rapid disassembly of caveolae. Cell 144:402–13
    [Google Scholar]
  147. Sowa G, Pypaert M, Sessa WC 2001. Distinction between signaling mechanisms in lipid rafts versus caveolae. PNAS 98:14072–77
    [Google Scholar]
  148. Stoeber M, Schellenberger P, Siebert CA, Leyrat C, Helenius A, Grunewald K 2016. Model for the architecture of caveolae based on a flexible, net-like assembly of Cavin1 and Caveolin discs. PNAS 113:E8069–78
    [Google Scholar]
  149. Stoeber M, Stoeck IK, Hanni C, Bleck CK, Balistreri G, Helenius A 2012. Oligomers of the ATPase EHD2 confine caveolae to the plasma membrane through association with actin. EMBO J 31:2350–64
    [Google Scholar]
  150. Tagawa A, Mezzacasa A, Hayer A, Longatti A, Pelkmans L, Helenius A 2005. Assembly and trafficking of caveolar domains in the cell: caveolae as stable, cargo-triggered, vesicular transporters. J. Cell Biol. 170:769–79
    [Google Scholar]
  151. Tagawa M, Ueyama T, Ogata T, Takehara N, Nakajima N et al. 2008. MURC, a muscle-restricted coiled-coil protein, is involved in the regulation of skeletal myogenesis. Am. J. Physiol. Cell Physiol. 295:C490–98
    [Google Scholar]
  152. Tang Z, Okamoto T, Boontrakulpoontawee P, Katada T, Otsuka AJ, Lisanti MP 1997. Identification, sequence, and expression of an invertebrate caveolin gene family from the nematode Caenorhabditis elegans. Implications for the molecular evolution of mammalian caveolin genes. J. Biol. Chem. 272:2437–45
    [Google Scholar]
  153. Thompson TC 1998. Metastasis-related genes in prostate cancer: the role of caveolin-1. Cancer Metastasis Rev 17:439–42
    [Google Scholar]
  154. Thompson TC, Tahir SA, Li L, Watanabe M, Naruishi K et al. 2010. The role of caveolin-1 in prostate cancer: clinical implications. Prostate Cancer Prostatic Dis 13:6–11
    [Google Scholar]
  155. Tillu VA, Kovtun O, McMahon KA, Collins BM, Parton RG 2015. A phosphoinositide-binding cluster in cavin1 acts as a molecular sensor for cavin1 degradation. Mol. Biol. Cell 26:3561–69
    [Google Scholar]
  156. Trushina E, Singh RD, Dyer RB, Cao S, Shah VH et al. 2006. Mutant huntingtin inhibits clathrin-independent endocytosis and causes accumulation of cholesterol in vitro and in vivo. Hum. Mol. Genet. 15:3578–91
    [Google Scholar]
  157. Walser PJ, Ariotti N, Howes M, Ferguson C, Webb R et al. 2012. Constitutive formation of caveolae in a bacterium. Cell 150:752–63
    [Google Scholar]
  158. Wanaski SP, Ng BK, Glaser M 2003. Caveolin scaffolding region and the membrane binding region of SRC form lateral membrane domains. Biochemistry 42:42–56
    [Google Scholar]
  159. Wickstrom SA, Lange A, Hess MW, Polleux J, Spatz JP et al. 2010. Integrin-linked kinase controls microtubule dynamics required for plasma membrane targeting of caveolae. Dev. Cell 19:574–88
    [Google Scholar]
  160. Xu XL, Wu LC, Du F, Davis A, Peyton M et al. 2001. Inactivation of human SRBC, located within the 11p15.5-p15.4 tumor suppressor region, in breast and lung cancers. Cancer Res 61:7943–49
    [Google Scholar]
  161. Yamaguchi T, Lu C, Ida L, Yanagisawa K, Usukura J et al. 2016. ROR1 sustains caveolae and survival signalling as a scaffold of cavin-1 and caveolin-1. Nat. Commun. 7:10060
    [Google Scholar]
  162. Yang L, Scarlata S 2017. Super-resolution visualization of caveola deformation in response to osmotic stress. J. Biol. Chem. 292:3779–88
    [Google Scholar]
  163. Yeow I, Howard G, Chadwick J, Mendoza-Topaz C, Hansen CG et al. 2017. EHD proteins cooperate to generate caveolar clusters and to maintain caveolae during repeated mechanical stress. Curr. Biol. 27:2951–62.e5
    [Google Scholar]
  164. Yu J, Bergaya S, Murata T, Alp IF, Bauer MP et al. 2006. Direct evidence for the role of caveolin-1 and caveolae in mechanotransduction and remodeling of blood vessels. J. Clin. Investig. 116:1284–91
    [Google Scholar]
  165. Zhang B, Peng F, Wu D, Ingram AJ, Gao B, Krepinsky JC 2007. Caveolin-1 phosphorylation is required for stretch-induced EGFR and Akt activation in mesangial cells. Cell. Signal. 19:1690–700
    [Google Scholar]
  166. Zhang G, Fang X, Guo X, Li L, Luo R et al. 2012. The oyster genome reveals stress adaptation and complexity of shell formation. Nature 490:49–54
    [Google Scholar]
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