Key Points
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Caveolae are a characteristic feature of mammalian cells. But what are the key functions of caveolae and how does caveolae dysfunction lead to disease?
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Caveolae form relatively stable domains at the plasma membrane that are enriched in lipid-raft markers and can function as carriers in the endocytic and exocytic pathways.
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The functions of caveolae remain puzzling; increasing evidence argues against a general signalling role and only a few of the originally postulated signalling functions remain solidly documented.
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Caveolae have been strongly linked to lipid regulation in adipocytes and other cell types.
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Caveolae have a role in mechanosensation in specific cell types.
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The underlying link between these functions might be a role in sensing membrane changes, a property that is reliant on the specific biophysical properties and lipid composition of the caveolar domain.
Abstract
Caveolae are a highly abundant but enigmatic feature of mammalian cells. They form remarkably stable membrane domains at the plasma membrane but can also function as carriers in the exocytic and endocytic pathways. The apparently diverse functions of caveolae, including mechanosensing and lipid regulation, might be linked to their ability to respond to plasma membrane changes, a property that is dependent on their specialized lipid composition and biophysical properties.
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Acknowledgements
We are extremely grateful to R. Stan, B. Sessa, J. Hancock, and members of the Parton and Simons laboratories for comments on the manuscript. The authors acknowledge the continuing support of the National Health and Medical Research Council of Australia (R.G.P.), the National Institutes of Health, USA (R.G.P.), the Max Planck Society (K.S.), Deutsche Forschungsgemeinschaft (K.S.) and the European Commission (K.S.). The Institute for Molecular Bioscience is a Special Research Centre of the Australian Research Council. We would also like to apologize to those researchers whose primary research could not be cited owing to space constraints.
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Glossary
- Stomatal diaphragm
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A specialized structure at the neck of caveolae in certain endothelial cells that consists of a central density and radial spikes, and is generated by the transmembrane protein PV1.
- Lipid rafts
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Small, heterogeneous, highly dynamic, sterol- and sphingolipid-enriched domains that are formed by lipid–lipid interactions that compartmentalize cellular processes. Small lipid rafts can be stabilized to form larger platforms through protein–protein and protein–lipid interactions.
- Signal recognition particle
-
(SRP). A complex of polypeptides and RNA involved in synthesis of proteins on membrane-bound ribosomes of the ER. SRP interaction with a specific signal on the nascent polypeptide dictates co-translational insertion of the protein into the ER.
- Detergent-resistant membrane
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(DRM). DRM fractions remain insoluble after cold Triton X-100 extraction. This is a crude biochemical measure for lipid-raft association.
- Exocytic caveolar carrier
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A carrier produced in the Golgi that resembles a fully formed caveola in caveolin density. We suggest the terms endocytic caveolar carrier and recycling caveolar carrier for budded caveolae or caveolae recycling back to the cell surface.
- SNAREs
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(Soluble N-ethylmaleimide-sensitive factor attachment-protein receptors). A protein family that consists of a cognate group of integral and peripheral membrane proteins that are required for bilayer recognition and fusion during membrane trafficking.
- Caveosome
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A neutral pH endosomal compartment that lacks classic endosomal markers but contains markers that are internalized through caveolae.
- Lipid droplet
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A lipid-storage organelle that comprises a core of triacylglycerol and/or cholesterol esters surrounded by a phospholipid monolayer.
- Mechanosensation
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The sensing of mechanical stimuli, for example stretch or flow, by cells.
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Parton, R., Simons, K. The multiple faces of caveolae. Nat Rev Mol Cell Biol 8, 185–194 (2007). https://doi.org/10.1038/nrm2122
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DOI: https://doi.org/10.1038/nrm2122
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