Key Points
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Caveolae, submicroscopic pits of the plasma membrane, consist of caveolin membrane proteins and cytoplasmic cavin proteins.
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Caveolae can bud from the plasma membrane, fuse with early endosomes and recycle back to the cell surface, or they can be turned over via a ubiquitylation-dependent mechanism and targeted to multivesicular bodies.
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Mutations in caveolins and cavins have been linked to diverse disease states, including cancer, lipodystrophy, cardiomyopathy and muscular dystrophies.
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The various diseases linked to caveolae dysfunction suggest a crucial cellular role in lipid regulation, membrane organization and in cell protection against physical stress.
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Flattening of caveolae in response to plasma membrane forces may provide a reservoir of membrane and activate signalling pathways through caveolins and cavins.
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Caveola dysfunction can influence a range of signalling pathways and lipid regulatory processes with widespread effects on cell function.
Abstract
Caveolae are submicroscopic, plasma membrane pits that are abundant in many mammalian cell types. The past few years have seen a quantum leap in our understanding of the formation, dynamics and functions of these enigmatic structures. Caveolae have now emerged as vital plasma membrane sensors that can respond to plasma membrane stresses and remodel the extracellular environment. Caveolae at the plasma membrane can be removed by endocytosis to regulate their surface density or can be disassembled and their structural components degraded. Coat proteins, called cavins, work together with caveolins to regulate the formation of caveolae but also have the potential to dynamically transmit signals that originate in caveolae to various cellular destinations. The importance of caveolae as protective elements in the plasma membrane, and as membrane organizers and sensors, is highlighted by links between caveolae dysfunction and human diseases, including muscular dystrophies and cancer.
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Acknowledgements
The authors thank R. Moreno-Vicente for help in drawing the schematics and A. Echarri, M. Montoya and M. Fernández-Rojo and other members of the Parton laboratory for critical reading of the manuscript. R.G.P. is supported by an National Health and Medical Research Council (NHMRC) Australia Fellowship. M.A.d.P. is supported by the Spanish Ministry of Economy and Competitiveness (MINECO) through grants SAF2011-25047 and CSD 2009–00016. The Centro Nacional de Investigaciones Cardiovasculares (CNIC) is supported by MINECO and the Pro-CNIC Foundation.
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Glossary
- Lipodystrophy
-
Abnormal fat metabolism associated with loss of adipose tissue.
- Clathrin-coated pits
-
Plasma membrane invaginations that are coated on their cytoplasmic face by a complex of coat proteins, including clathrin. Best-characterized internalization mechanism for surface receptors, ligands and solutes.
- Multivesicular bodies
-
(MVBs). Endosomal compartment that contains internal vesicles in which membrane proteins destined for lysosomal degradation are concentrated.
- Metaphase
-
Phase of mitosis in which chromosomes are aligned along the equatorial plane of the spindle.
- Ubiquitylation
-
Modification of a protein by addition of a polypeptide, ubiquitin. This post- translational modification acts as a signal to mark a protein for internalization or degradation.
- Stress fibres
-
Contractile actomyosin bundles that are formed by actin filaments, crosslinking proteins (that bind two or more filaments together) and myosin motors.
- Mechanosensing
-
Mechanisms that cells use to detect and respond to forces.
- Focal adhesion
-
Large and dynamic protein complex (composed of integrins and cytoskeletal and signalling molecules) through which the cytoskeleton connects to the extracellular matrix to transmit both mechanical force and regulatory signals.
- Store-operated calcium entry
-
(SOCE). A calcium entry mechanism that is activated by depletion of internal calcium stores in the endoplasmic reticulum.
- Membrane rafts
-
Small, heterogeneous, highly dynamic, sterol- and sphingolipid-enriched domains that are formed by lipid–lipid interactions and that compartmentalize cellular processes. Small rafts can be stabilized to form larger platforms through protein–protein and protein–lipid interactions.
- Eisosome
-
Stable Pil1- and Lsp1-positive domain of the yeast plasma membrane implicated in mechanosensation and lipid regulation.
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Parton, R., del Pozo, M. Caveolae as plasma membrane sensors, protectors and organizers. Nat Rev Mol Cell Biol 14, 98–112 (2013). https://doi.org/10.1038/nrm3512
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DOI: https://doi.org/10.1038/nrm3512
