Cells Respond to Mechanical Stress by Rapid Disassembly of Caveolae

Abstract

SUMMARY The precise role of caveolae, the characteristic plasma membrane invaginations present in many cells, still remains debated. The high density of caveolae in cells experiencing mechanical stress led us to investigate their role in membrane-mediated mechanical response. Acute mechanical stress induced by cell osmotic swelling or by uniaxial stretching results in the immediate disappearance of caveolae, which is associated with a reduced caveolin/Cavin1 interaction, and an increase of free caveolins at the plasma membrane. Tether pulling force measurements in live cells and in plasma membrane spheres demonstrate that caveola flattening and disassembly is the primary actin and ATP-independent cell response which buffers membrane tension surges during mechanical stress. Conversely, stress release leads to complete caveola reassembly in an actin and ATP-dependent process. The absence of a functional caveola reservoir in myotubes from muscular dystrophic patients enhanced membrane fragility under mechanical stress. Our findings support a new role for caveolae as a physiological membrane reservoir that allows cells to quickly accommodate sudden and acute mechanical stresses.

Molecular Characterization of Caveolin-induced Membrane Curvature

“…F, schematic of Cav1 membrane association after introduction of the negatively charged residue. caveola formation, it is possible that the extrusion of this site from the membrane is a critical step in destabilizing the caveola unit in response to a mechanical stress (6). This hypothesis is strengthened by the observation that the S80E point mutant cannot form caveolae (13) and this region is masked by the membrane in mature PM-associated caveolae but exposed after the disruption of caveola structure by cholesterol depletion (47).…”

“…Caveolae are small (50 -80 nm in diameter) bulb-shaped invaginations of the plasma membrane (PM) 4 that function in a multitude of fundamental cellular processes, including the mechanosensation response, cholesterol homeostasis, and the regulation of cellular signaling (1)(2)(3)(4)(5)(6)). An essential structural protein of caveolae is Caveolin-1 (Cav1) (7), a 22-kDa cholesterol-binding membrane protein that has been hypothesized to adopt a hairpin-like structure in the membrane, with both the N and C termini facing the cellular cytoplasm (8).…”

The arginylation branch of the N-end rule pathway positively regulates cellular autophagic flux and clearance of proteotoxic proteins

“…The levels of many DEPs were confirmed to behave as conjectured from the quantitative mass spectrometry. For example, CAV1/caveolin-1, whose function involves the modulation of mechanical stress and oxidative stress in cells, 58,59 were significantly upregulated after PCA treatment, along with the endogenous Arg/ N-end rule substrate RGS4 (Fig. 5C).…”

Loss of Caveolin-1 Impairs Retinal Function Due to Disturbance of Subretinal Microenvironment

“…in mechanotransduction (3)(4)(5)). The inner leaflet of caveolae are coated with oligomers of 21-24-kDa integral membrane proteins called caveolins (6).…”