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Sci. Signal., 15 February 2011
Vol. 4, Issue 160, p. ec49
[DOI: 10.1126/scisignal.4160ec49]

EDITORS' CHOICE

Cell Biology Providing a Membrane Reservoir

Elizabeth M. Adler

Science Signaling, AAAS, Washington, DC 20005, USA

Mechanical stresses can lead to changes in cell membrane tension, thereby affecting the function of membrane lipids and proteins. For instance, cell swelling under hypoosmotic conditions will increase membrane tension unless additional membrane is incorporated into the cell surface (see Mayor). Noting that caveolae (flask-shaped invaginations of the plasma membrane) are abundant in cells exposed to mechanical stress, Sinha et al. explored their role in the acute response to mechanical stress. When HeLa cells stably transfected with fluorescently labeled caveolin-1 (Cav1, a scaffolding protein that is a major component of the caveolar membrane) were exposed to hypoosmotic medium, they underwent an initial increase in cell volume (during the first 5 minutes), followed by a slow decrease. Total internal reflection microscopy analysis during the initial period of increased volume revealed a decrease in caveolar number that correlated with severity of the shock. Loss of caveolae, which was also apparent in cells stretched with a mechanical device, was confirmed by electron microscopy (EM) in mouse lung endothelial cells (MLECs, a class of cells exposed to shear stress in vivo) undergoing hypoosmotic shock. Various approaches (immuno-EM analysis of Cav1 localization; fluorescence lifetime imaging microscopy analysis of the association of Cav1 with Cavin1, which maintains caveolar invagination; and fluorescence recovery after photobleaching analysis of Cav1 diffusion) indicated that hypoosmotic shock disrupted the Cav1-Cavin1 interaction and led to caveolar flattening. Using a tether-pulling technique to monitor membrane tension, the authors determined that, whereas hypoosmotic shock had little effect on membrane tension in wild-type MLECs, it increased membrane tension in MLECs lacking Cav1 and in cholesterol-depleted cells (in which caveolae were already flattened). Moreover, hypoosmotic shock failed to increase membrane tension in wild-type human myotubes but did so in myotubes bearing a mutant form of Cav3 (the muscle isoform of caveolin) associated with a form of muscular dystrophy (P28L Cav3), which, unlike wild-type Cav3, failed to localize to the plasma membrane. After return to isoosmotic medium, caveolae reassembled within minutes. Although caveolar flattening and the ensuing buffering of membrane tension during hypoosmotic shock occurred independently of ATP and of the actin cytoskeleton, reassembly of caveolae after return to isoosmotic medium required ATP and was promoted by cytochalasin D, which blocks actin dynamics. Thus, caveolae appear to act as a membrane reservoir that can buffer variations in membrane tension during the response to acute mechanical stress.

B. Sinha, D. Köster, R. Ruez, P. Gonnord, M. Bastiani, D. Abankwa, R. V. Stan, G. Butler-Browne, B. Vedie, L. Johannes, N. Morone, R. G. Parton, G. Raposo, P. Sens, C. Lamaze, P. Nassoy, Cells respond to mechanical stress by rapid disassembly of caveolae. Cell 144, 402–413 (2011). [PubMed]

S. Mayor, Need tension relief fast? Try caveolae. Cell 144, 323–324 (2011). [PubMed]

Citation: E. M. Adler, Providing a Membrane Reservoir. Sci. Signal. 4, ec49 (2011).



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