Membrane Rafts and Caveolae

Abstract

The plasma membrane does more than serve as a barrier between the contents of the cell and the extracellular space. It is a highly organized structure which contains fatty acids, cholesterol and a variety of proteins and is functionally important in trafficking cellular signals. The concept of organized structures or domains within the plasma membrane has proven invaluable to understanding how the plasma membrane interacts with the surrounding environment. One class of these domains is lipid rafts which have been shown to organize and regulate signalling platforms. Caveolae are a subset of lipid rafts which contain specific proteins and lipids that aid in the regulation of signalling processes differently from other domains. Purification techniques have made it possible to study the biochemistry of lipid rafts and caveolae and to gain a better understanding of their roles in signal transduction.

Keywords: lipid rafts; caveolae; signalling; cholesterol; membranes

References

Aboulaich N, Ortegren U, Vener AV and Stralfors P (2006) Association and insulin regulated translocation of hormone‐sensitive lipase with PTRF. Biochemical and Biophysical Research Communications 350: 657–661.

Anderson RG (1998) The caveolae membrane system. Annual Review of Biochemistry 67: 199–225.

Arcaro A, Aubert M, Espinosa del Hierro ME et al. (2007) Critical role for lipid raft‐associated Src kinases in activation of PI3K‐Akt signalling. Cellular Signalling 19: 1081–1092.

Babiychuk EB, Monastyrskaya K, Burkhard FC, Wray S and Draeger A (2002) Modulating signaling events in smooth muscle: cleavage of annexin 2 abolishes its binding to lipid rafts. FASEB Journal 16: 1177–1184.

Becher A and McIlhinney RA (2005) Consequences of lipid raft association on G‐protein‐coupled receptor function. Biochemical Society Symposium 72: 151–164.

Bhatnagar A, Sheffler DJ, Kroeze WK, Compton‐Toth B and Roth BL (2004) Caveolin‐1 interacts with 5‐HT2A serotonin receptors and profoundly modulates the signaling of selected Galphaq‐coupled protein receptors. Journal of Biological Chemistry 279: 34614–34623.

Blair A, Shaul PW, Yuhanna IS, Conrad PA and Smart EJ (1999) Oxidized low density lipoprotein displaces endothelial nitric oxide synthase (eNOS) from plasmalemmal caveolae and impairs eNOS activation. Journal of Biological Chemistry 274: 32512–32519.

Brown DA and Rose JK (1992) Sorting of GPI‐anchored proteins to glycolipid‐enriched membrane subdomains during transport to the apical cell surface. Cell 68: 533–544.

Chambliss KL, Yuhanna IS, Mineo C et al. (2000) Estrogen receptor alpha and endothelial nitric oxide synthase are organized into a function signaling module in caveolae. Circulation Research 87: E44–E52.

Cohen RA (1995) The role of nitric oxide and other endothelium‐derived vasoactive substances in vascular disease. Progress in Cardiovascular Disease 38: 105–128.

Couet J, Li S, Okamoto T, Ikezu T and Lisanti MP (1997) Identification of peptide and protein ligands for the caveolin‐scaffolding domain. Implications for the interaction of caveolin with caveolae‐associated proteins. Journal of Biological Chemistry 272: 6525–6533.

Davis ME, Cai H, McCann L, Fukai T and Harrison DG (2003) Role of c‐Src in regulation of endothelial nitric oxide synthase expression during exercise training. American Journal of Physiology, Heart and Circulatory Physiology 284: H1449–H1453.

Dietzen DJ, Hastings WR and Lublin DM (1995) Caveolin is palmitoylated on multiple cysteine residues. Palmitoylation is not necessary for localization of caveolin to caveolae. Journal of Biological Chemistry 270: 6838–6842.

Drab M, Verkade P, Elger M et al. (2001) Loss of caveolae, vascular dysfunction, and pulmonary defects in caveolin‐1 gene‐disrupted mice. Science 293: 2449–2452.

Feron O, Saldana F, Michel JB and Michel T (1998) The endothelial nitric‐oxide synthase‐caveolin regulatory cycle. Journal of Biological Chemistry 273: 3125–3128.

Fielding PE, Nagao K, Hakamata H, Chimini G and Fielding CJ (2000) A two‐step mechanism for free cholesterol and phospholipid efflux from human vascular cells to apolipoprotein A‐1. Biochemistry 39: 14113–14120.

Fridriksson EK, Shipkova PA, Sheets ED et al. (1999) Quantitative analysis of phospholipids in functionally important membrane domains from RBL‐2H3 mast cells using tandem high‐resolution mass spectrometry. Biochemistry 38: 8056–8063.

Fujimoto T, Kogo H, Nomura R and Une T (2000) Isoforms of caveolin‐1 and caveolar structure. Journal of Cell Science 113(Pt 19): 3509–3517.

Galbiati F, Engelman JA, Volonte D et al. (2001) Caveolin‐3 null mice show a loss of caveolae, changes in the microdomain distribution of the dystrophin‐glycoprotein complex, and t‐tubule abnormalities. Journal of Biological Chemistry 276: 21425–21433.

Glenney Jr JR and Soppet D (1992) Sequence and expression of caveolin, a protein component of caveolae plasma membrane domains phosphorylated on tyrosine in Rous sarcoma virus‐transformed fibroblasts. Proceedings of the National Academy of Sciences of the USA 89: 10517–10521.

Graf GA, Connell PM, van der Westhuyzen DR and Smart EJ (1999) The class B, type I scavenger receptor promotes the selective uptake of high density lipoprotein cholesterol ethers into caveolae. Journal of Biological Chemistry 274: 12043–12048.

Hisamoto K, Ohmichi M, Kurachi H et al. (2001) Estrogen induces the Akt‐dependent activation of endothelial nitric‐oxide synthase in vascular endothelial cells. Journal of Biological Chemistry 276: 3459–3467.

Kawamura S, Miyamoto S and Brown JH (2003) Initiation and transduction of stretch‐induced RhoA and Rac1 activation through caveolae: cytoskeletal regulation of ERK translocation. Journal of Biological Chemistry 278: 31111–31117.

Kogo H, Ito S, Moritoki Y, Kurahashi H and Fujimoto T (2006) Differential expression of caveolin‐3 in mouse smooth muscle cells in vivo. Cell Tissue Research 324: 291–300.

Kuhlencordt PJ, Gyurko R, Han F et al. (2001) Accelerated atherosclerosis, aortic aneurysm formation, and ischemic heart disease in apolipoprotein E/endothelial nitric oxide synthase double‐knockout mice. Circulation 104: 448–454.

Kurzchalia TV, Dupree P and Monier S (1994) VIP21‐Caveolin, a protein of the trans‐Golgi network and caveolae. FEBS Letters 346: 88–91.

Lee H, Woodman SE, Engelman JA et al. (2001) Palmitoylation of caveolin‐1 at a single site (Cys‐156) controls its coupling to the c‐Src tyrosine kinase: targeting of dually acylated molecules (GPI‐linked, transmembrane, or cytoplasmic) to caveolae effectively uncouples c‐Src and caveolin‐1 (TYR‐14). Journal of Biological Chemistry 276: 35150–35158.

Liu P and Anderson RG (1995) Compartmentalized production of ceramide at the cell surface. Journal of Biological Chemistry 270: 27179–27185.

Marguet D, Lenne PF, Rigneault H and He HT (2006) Dynamics in the plasma membrane: how to combine fluidity and order. EMBO Journal 25: 3446–3457.

Munro S (2003) Lipid rafts: elusive or illusive? Cell 115: 377–388.

Oh P and Schnitzer JE (1999) Immunoisolation of caveolae with high affinity antibody binding to the oligomeric caveolin cage. Journal of Biological Chemistry 274: 23144–23154.

Palade GE (1953) Fine structure of blood capillaries. Journal of Applied Physics 24: 1424.

Parton RG (1996) Caveolae and caveolins. Current Opinion in Cell Biology 8: 542–548.

Parton RG and Richards AA (2003) Lipid rafts and caveolae as portals for endocytosis: new insights and common mechanisms. Traffic 4: 724–738.

Prior IA, Harding A, Yan J et al. (2001) GTP‐dependent segregation of H‐ras from lipid rafts is required for biological activity. Nature Cell Biology 3: 368–375.

Radel C and Rizzo V (2005) Integrin mechanotransduction stimulates caveolin‐1 phosphorylation and recruitment of Csk to mediate actin reorganization. American Journal of Physiology, Heart and Circulatory Physiology 288: H936–H945.

Rajendran L, Masilamani M, Solomon S et al. (2003) Asymmetric localization of flotillins/reggies in preassembled platforms confers inherent polarity to hematopoietic cells. Proceedings of the National Academy of Sciences of the USA 100: 8241–8246.

Rajendran L and Simons K (2005) Lipid rafts and membrane dynamics. Journal of Cell Science 118: 1099–1102.

Razani B, Schlegel A and Lisanti MP (2000) Caveolin proteins in signaling, oncogenic transformation and muscular dystrophy. Journal of Cell Science 113(Pt 12): 2103–2109.

Razani B, Wang XB, Engelman JA et al. (2002) Caveolin‐2‐deficient mice show evidence of severe pulmonary dysfunction without disruption of caveolae. Molecular and Cellular Biology 22: 2329–2344.

Rothberg KG, Heuser JE, Donzell WC et al. (1992) Caveolin, a protein component of caveolae membrane coats. Cell 68: 673–682.

Rothberg KG, Ying YS, Kamen BA and Anderson RG (1990) Cholesterol controls the clustering of the glycophospholipid‐anchored membrane receptor for 5‐methyltetrahydrofolate. Journal of Cell Biology 111: 2931–2938.

Roy S, Plowman S, Rotblat B et al. (2005) Individual palmitoyl residues serve distinct roles in H‐ras trafficking, microlocalization, and signaling. Molecular and Cellular Biology 25: 6722–6733.

Schnitzer JE, Oh P and McIntosh DP (1996) Role of GTP hydrolysis in fission of caveolae directly from plasma membranes. Science 274: 239–242.

Sedding DG, Hermsen J, Seay U et al. (2005) Caveolin‐1 facilitates mechanosensitive protein kinase B (Akt) signaling in vitro and in vivo. Circulation Research 96: 635–642.

Shaul PW, Smart EJ, Robinson LJ et al. (1996) Acylation targets endothelial nitric‐oxide synthase to plasmalemmal caveolae. Journal of Biological Chemistry 271: 6518–6522.

Simons K and Toomre D (2000) Lipid rafts and signal transduction. Nature Reviews. Molecular Cell Biology 1: 31–39.

Simons K and Vaz WL (2004) Model systems, lipid rafts, and cell membranes. Annual Review of Biophysics and Biomolecular Structure 33: 269–295.

Smart EJ, Ying YS, Conrad PA and Anderson RG (1994) Caveolin moves from caveolae to the Golgi apparatus in response to cholesterol oxidation. Journal of Cell Biology 127: 1185–1197.

Smart EJ, Ying YS, Mineo C and Anderson RG (1995) A detergent‐free method for purifying caveolae membrane from tissue culture cells. Proceedings of the National Academy of Sciences of the USA 92: 10104–10108.

Song KS, Li S, Okamoto T et al. (1996) Co‐purification and direct interaction of Ras with caveolin, an integral membrane protein of caveolae microdomains. Detergent‐free purification of caveolae microdomains. Journal of Biological Chemistry 271: 9690–9697.

Song KS, Sargiacomo M, Galbiati F, Parenti M and Lisanti MP (1997) Targeting of a G alpha subunit (Gi1 alpha) and c‐Src tyrosine kinase to caveolae membranes: clarifying the role of N‐myristoylation. Cellular and Molecular Biology 43: 293–303.

Stan RV (2002) Structure and function of endothelial caveolae. Microscopy Research and Technique 57: 350–364.

Swamy MJ, Ciani L, Ge M et al. (2006) Coexisting domains in the plasma membranes of live cells characterized by spin‐label ESR spectroscopy. Biophysical Journal 90: 4452–4465.

Thiele C, Hannah MJ, Fahrenholz F and Huttner WB (2000) Cholesterol binds to synaptophysin and is required for biogenesis of synaptic vesicles. Nature Cell Biology 2: 42–49.

Uittenbogaard A, Shaul PW, Yuhanna IS, Blair A and Smart EJ (2000) High density lipoprotein prevents oxidized low density lipoprotein‐induced inhibition of endothelial nitric‐oxide synthase localization and activation in caveolae. Journal of Biological Chemistry 275: 11278–11283.

Uittenbogaard A and Smart EJ (2000) Palmitoylation of caveolin‐1 is required for cholesterol binding, chaperone complex formation, and rapid transport of cholesterol to caveolae. Journal of Biological Chemistry 275: 25595–25599.

Uittenbogaard A, Ying Y and Smart EJ (1998) Characterization of a cytosolic heat‐shock protein‐caveolin chaperone complex. Involvement in cholesterol trafficking. Journal of Biological Chemistry 273: 6525–6532.

Vinten J, Voldstedlund M, Clausen H et al. (2001) A 60‐kDa protein abundant in adipocyte caveolae. Cell Tissue Research 305: 99–106.

Yamada E (1955) The fine structure of the gall bladder epithelium of the mouse. Journal of Biophysical and Biochemical Cytology 1: 445–458.

Further Reading

Everson WV and Smart EJ (2005) Caveolae and the regulation of cellular cholesterol homeostasis. In: Lisanti MP and Frank PG (eds) Advances in Molecular and Cell Biology series: Caveolae and Lipid Rafts: Roles in Signal Transduction and the Pathogenesis of Human Disease. vol. 36, pp. 37–55. San Diego, CA: Elsevier Academic Press.

Lajoie P and Nabi IR (2007) Regulation of raft‐dependent endocytosis. Journal of cellular and molecular medicine 11: 644–653.

Smart EJ, Graf GA, McNiven MA et al. (1999) Caveolins, liquid‐ordered domains, and signal transduction. Molecular and cellular biology 19: 7289–7304.

Thomas CM and Smart EJ (2008) Caveolae structure and function. Journal of cellular and molecular medicine 12: 796–809.

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Thomas, Candice M, and Smart, Eric J(Sep 2008) Membrane Rafts and Caveolae. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0021022]