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704 Cell 154, August 1, 2013 ©2013 Elsevier Inc. DOI http://dx.doi.org/10.1016/j.cell.2013.07.009 See online version for legend and references.

704.e1 Cell 154, August 1, 2013 ©2013 Elsevier Inc. DOI http://dx.doi.org/10.1016/j.cell.2013.07.009

SnapShot: Caveolae, Caveolins, and CavinsNicholas Ariotti and Robert G. PartonInstitute for Molecular Bioscience, University of Queensland, St. Lucia, QLD 4072, Australia

Caveolae, submicroscopic bulb-shaped plasma membrane pits, are an abundant feature of many mammalian cells (Parton and del Pozo, 2013). Caveolae and the major proteins of caveolae, caveolins (Rothberg et al., 1992), and cavins (Hill et al., 2008), are linked to a number of human diseases such as muscular dystrophy, cardiomyopathy, and lipodys-trophy (see Glossary) (Bruno et al., 1993; Fernández et al., 2006; Hayashi et al., 2009).

As illustrated, caveolae show a striking tissue distribution with abundant caveolae in some cell types but an apparent absence from others. This is paralleled by highly variable expression of caveolins and cavins from tissue to tissue and the association of caveolar dysfunction with specific disease conditions (Allen et al., 2011; Bruno et al., 1993; Hansen et al., 2013; Hayashi et al., 2009).

Caveolae are generated at the plasma membrane as caveolins and cavins come together to form the characteristic curved microdomain (Parton and del Pozo, 2013). They can bud from the plasma membrane, and the budded caveolae then fuse with early endosomes. The bulk of the caveolar components are then recycled back to the cell surface, but caveolae can also be disassembled and the components degraded after incorporation into the intralumenal vesicles of multivesicular late endosomal compartments (Parton and del Pozo, 2013). Caveolae at the plasma membrane can be flattened and their components dispersed in response to mechanical stress at the plasma membrane, allowing mechanoprotection or expansion of the plasma membrane (Sinha et al., 2011). Though the mechanism remains elusive, caveolae and caveolins are also known to regulate cellular signaling pathways (García-Cardeña et al., 1997) by direct or indirect means.

Glossary

Caveolae: 50–80 nm diameter invagination of the plasma membrane, characterized by lack of coat by conventional electron microscopy and presence of caveolins

Caveolins (Cav1, Cav2, and Cav3): major membrane proteins of caveolae

Cavins, PTRF/Cavin1, SDR/Cavin2, PRKCDABP/SRBC/Cavin3, and MURC/Cavin4: peripheral membrane proteins of caveolae

Muscular dystrophy: a group of muscle diseases associated with weakness of the muscular system

Rippling muscle disease: sporadic disorder associated with muscle contractions producing a visible rippling effect; can be associated with muscle pain

Lipodystrophy: abnormal or degeneration of adipose tissue

Cardiomyopathy: disease of the heart muscle

Mechanosensation: physiological response to mechanical stimulation

Lipotoxicity: cellular dysfunction and death caused by accumulation of lipids

T (transverse) tubules: tubular invaginations of the muscle plasma membrane (sarcolemma) allowing propagation of action potentials to the muscle interior

references

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Bruno, C., Sotgia, F., Gazzerro, E., Minetti, C., and Lisanti, M.P. (1993). Caveolinopathies. In GeneReviews, R.A. Pagon, M.P. Adam, T.D. Bird, eds. (University of Washington Press), http://www.ncbi.nlm.nih.gov/books/NBK1385/.

Fernández, M.A., Albor, C., Ingelmo-Torres, M., Nixon, S.J., Ferguson, C., Kurzchalia, T., Tebar, F., Enrich, C., Parton, R.G., and Pol, A. (2006). Science 313, 1628–1632.

García-Cardeña, G., Martasek, P., Masters, B.S., Skidd, P.M., Couet, J., Li, S., Lisanti, M.P., and Sessa, W.C. (1997). J. Biol. Chem. 272, 25437–25440.

Hansen, C.G., Shvets, E., Howard, G., Riento, K., and Nichols, B.J. (2013). Nat. Commun. 4, 1831.

Hayashi, Y.K., Matsuda, C., Ogawa, M., Goto, K., Tominaga, K., Mitsuhashi, S., Park, Y.E., Nonaka, I., Hino-Fukuyo, N., Haginoya, K., et al. (2009). J. Clin. Invest. 119, 2623–2633.

Hill, M.M., Bastiani, M., Luetterforst, R., Kirkham, M., Kirkham, A., Nixon, S.J., Walser, P., Abankwa, D., Oorschot, V.M., Martin, S., et al. (2008). Cell 132, 113–124.

Parton, R.G., and del Pozo, M.A. (2013). Nat. Rev. Mol. Cell Biol. 14, 98–112.

Rothberg, K.G., Heuser, J.E., Donzell, W.C., Ying, Y.S., Glenney, J.R., and Anderson, R.G. (1992). Cell 68, 673–682.

Sinha, B., Köster, D., Ruez, R., Gonnord, P., Bastiani, M., Abankwa, D., Stan, R.V., Butler-Browne, G., Vedie, B., Johannes, L., et al. (2011). Cell 144, 402–413.