The Forces that Shape Caveolae

Sens, Pierre; Turner, Matthew S.

doi:10.1002/3527608079.ch2

Cited by 7 publications

(6 citation statements)

References 36 publications

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“…The key feature which distinguishes caveolae from other lipid rafts is the presence of caveolin; caveolins are 18-22 kDa proteins which insert asymmetrically into the plasma membrane in a hairpin-like conformation, with both N and C termini found intracellularly (Figure 1B). Caveolin is responsible, in part, for the typical flask-like morphology of the caveola through this asymmetrical membrane insertion and its tendency to cluster into oligomers, both of which promote membrane curvature [3]. Within the last decade, another group of proteins, the cavins, have been shown to contribute to caveolar biogenesis and function (see [4] for a recent review).…”

Section: Introductionmentioning

confidence: 99%

Caveolae create local signalling domains through their distinct protein content, lipid profile and morphology

Harvey¹,

Calaghan²

2012

Journal of Molecular and Cellular Cardiology

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Compartmentation of signalling allows multiple stimuli to achieve diverse cellular responses with only a limited pool of second messengers. This spatial control of signalling is achieved, in part, by cellular structures which bring together elements of a particular cascade. One such structure is the caveola, a flask-shaped lipid raft. Caveolae are well-recognised as signalosomes, platforms for assembly of signalling complexes of receptors, effectors and their targets, which can facilitate efficient and specific cellular responses. Here we extend this simple model and present evidence to show how the protein and lipid profiles of caveolae, as well as their characteristic morphology, define their roles in creating local signalling domains in the cardiac myocyte.

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Section: Introductionmentioning

confidence: 99%

Caveolae create local signalling domains through their distinct protein content, lipid profile and morphology

Harvey¹,

Calaghan²

2012

Journal of Molecular and Cellular Cardiology

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“…They represent a specialised form of lipid raft, characterised by the presence of the small protein caveolin, which inserts into the inner leaflet of the membrane via a hairpin loop [1] . The assymetrical insertion of caveolin, and its tendency to cluster into oligomers gives caveolae their typical flask-like shape [2] , [3] . Caveolin (Cav) is expressed as 3 major isoforms: Cav 1 and 2 (ubiquitously expressed) and Cav 3 (muscle-specific).…”

Section: Introductionmentioning

confidence: 99%

Caveolae Act as Membrane Reserves Which Limit Mechanosensitive ICl,swell Channel Activation during Swelling in the Rat Ventricular Myocyte

2009

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BackgroundMany ion channels are preferentially located in caveolae where compartmentalisation/scaffolding with signal transduction components regulates their activity. Channels that are mechanosensitive may be additionally dependent on caveolar control of the mechanical state of the membrane. Here we test which mechanism underlies caveolar-regulation of the mechanosensitive I Cl,swell channel in the adult cardiac myocyte.Methodology/Principal FindingsRat ventricular myocytes were exposed to solution of 0.02 tonicity (T; until lysis), 0.64T for 10–15 min (swelling), and/or methyl-β-cyclodextrin (MBCD; to disrupt caveolae). MBCD and 0.64T swelling reduced the number of caveolae visualised by electron microscopy by 75 and 50% respectively. MBCD stimulated translocation of caveolin 3 from caveolae-enriched buoyant membrane fractions, but both caveolin 1 and 3 remained in buoyant fractions after swelling. I Cl,swell inhibition in control cells decreased time to half-maximal volume (t 0.5,vol; 0.64T), consistent with a role for I Cl,swell in volume regulation. MBCD-treated cells showed reduced time to lysis (0.02T) and t 0.5,vol (0.64T) compared with controls. The negative inotropic response to swelling (an index of I Cl,swell activation) was enhanced by MBCD.Conclusions/SignificanceThese data show that disrupting caveolae removes essential membrane reserves, which speeds swelling in hyposmotic conditions, and thereby promotes activation of I Cl,swell. They illustrate a general principle whereby caveolae as a membrane reserve limit increases in membrane tension during stretch/swelling thereby restricting mechanosensitive channel activation.

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“…Based on these and many other experimental results and on theoretical considerations, it was suggested that laterally mobile nanodomains that detach from the membrane skeleton may sort into curved or flat membrane regions depending on their intrinsic shape and/or direct interactions between the nanodomains [9,15,70]. Much experimental and theoretical evidence indicates the importance of nanodomains in the process of membrane budding and microvesiculation [11,15,18,[72][73][74], and references therein]. It was shown that the membranes of Ca 2+ -induced microvesicles and erythrocyte nanovesicles contain lipid rafts [74,75], while the caveolae of Ω-shaped membrane invaginations are enriched with cholesterol and sfingomielin, known constituents of lipid rafts [11,[76][77][78].…”

Section: Curvature-mediated Lateral Redistribution Of Membrane Constimentioning

confidence: 99%

“…Much experimental and theoretical evidence indicates the importance of nanodomains in the process of membrane budding and microvesiculation [11,15,18,[72][73][74], and references therein]. It was shown that the membranes of Ca 2+ -induced microvesicles and erythrocyte nanovesicles contain lipid rafts [74,75], while the caveolae of Ω-shaped membrane invaginations are enriched with cholesterol and sfingomielin, known constituents of lipid rafts [11,[76][77][78]. Also, it was indicated that the assembly of cholesterol-based lipid microdomains is required for the biogenesis of secretory vesicles from the transGolgi network in the neuroendocrine cells [79,80].…”

Section: Curvature-mediated Lateral Redistribution Of Membrane Constimentioning

confidence: 99%

“…The nanotubes and microvesicles are small enough to be classified as nanostructures, with their radius ranging from fifty to a few hundred nm. An important feature of the formation mechanisms for both is that they are preceeded by lateral reorganization of the membrane into rafts and nanodomains [10][11][12][13][14][15]. As this process is mediated by the local curvature of the membrane, which is in turn determined by the local composition of the constituents, it is the intrinsic shape of the constituents and their interactions with the neighboring molecules [9,11,[15][16][17][18][19][20] that determine whether microvesiculation or tubulation of the membrane occurs [9,10,[13][14][15].…”

Section: Introductionmentioning

confidence: 99%

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Mechanisms for the formation of membranous nanostructures in cell-to-cell communication

Schara¹,

Janša

Šuštar

et al. 2009

Cellular and Molecular Biology Letters

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Cells interact by exchanging material and information. Two methods of cell-to-cell communication are by means of microvesicles and by means of nanotubes. Both microvesicles and nanotubes derive from the cell membrane and are able to transport the contents of the inner solution. In this review, we describe two physical mechanisms involved in the formation of microvesicles and nanotubes: curvature-mediated lateral redistribution of membrane components with the formation of membrane nanodomains; and plasmamediated attractive forces between membranes. These mechanisms are clinically relevant since they can be affected by drugs. In particular, the underlying mechanism of heparin's role as an anticoagulant and tumor suppressor is the suppression of microvesicluation due to plasma-mediated attractive interaction between membranes.

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The Forces that Shape Caveolae

Cited by 7 publications

References 36 publications

Caveolae create local signalling domains through their distinct protein content, lipid profile and morphology

Caveolae create local signalling domains through their distinct protein content, lipid profile and morphology

Caveolae Act as Membrane Reserves Which Limit Mechanosensitive ICl,swell Channel Activation during Swelling in the Rat Ventricular Myocyte

Mechanisms for the formation of membranous nanostructures in cell-to-cell communication

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