Snapshot: Caveolae, Caveolins, and Cavins Nicholas Ariotti and Robert G

Home , Caveolae, Caveolin, Caveolin 3, EHD2

704 Cell SnapShot: Caveolae, Caveolins, and Cavins Nicholas Ariotti and Robert G. Parton uut1 03©03Esve n. DOI http://dx.doi.org/10.1016/j.cell.2013.07.009 154, August 1,2013©2013 Elsevier Inc. Institute for Molecular Bioscience, University of Queensland, St. Lucia, QLD 4072, Australia

ORGAN/ COMPONENTS DISEASE AND TISSUE-SPECIFIC CAVEOLAR COMPLEXES TISSUE CELLULAR PROCESS

Rippling muscle disease Caveolin3 Striated muscle ﬁber Limb girdle muscular dystrophy Muscle Cavin1 skeletal and Cardiomyopathy Cavin4 cardiac Mechanoprotection Cav1 (heart) T-tubule formation

Caveolin1 Lipodystrophy Caveolin2 Lipotoxicity Adipose Cavin1 Fatty acid regulation tissue Cavin2 Insulin signaling Cavin3 Mechanoprotection

Atherosclerosis Caveolin1 In ammation Caveolin2 Lung Pulmonary hypertension and other Cavin1 Adipocyte Pulmonary brosis endothelia Cavin2 Mechanosensation Cavin3 Signaling

Fatty liver Hepatocellular carcinoma Caveolin1 LIPID DROPLET Liver Lipid metabolism Caveolin2 Carbohydrate metabolism Liver regeneration

Caveolin1 Autism Brain Cavin1 Schizophrenia Cavin3 LOW EXPRESSION HIGH EXPRESSION Capillary GENERAL CELLULAR CONTEXT

ENDOCYTOSIS MECHANOPROTECTION SIGNALING See online version for legend and references. Membrane stretch LUMEN

Cavin complex Caveola

EHD2 eNOS Ca2+ inactive Rab5 Dynamin2 EARLY ENDOSOME Intracellular targets MVB/ Caveolin 1 Caveolin 2 Caveolin 3 Dynamin2 late endosome

eNOS Cavin1 Cavin2 Cavin3 Cavin4 eNOS EHD2 active SnapShot: Caveolae, Caveolins, and Cavins Nicholas Ariotti and Robert G. Parton Institute 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 lipodystrophy (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

Allen, J.A., Yadav, P.N., Setola, V., Farrell, M., and Roth, B.L. (2011). Transcult. Psychiatry 1, e33.

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.