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NOTE: CANCELED. How may a membrane protein sense small cell volume perturbations?

NOTE: CANCELED

Seminar by Else K Hoffmann, Institute of Molecular Biology, University of Copenhagen.

Abstract
Changes in intra- or extracellular osmolarities during physiological or pathophysiological conditions elicit rapid changes in cell volume, followed by regulatory volume changes – volume regulation. The effectors (membrane transporters and channels) of volume regulation and the signalling mechanisms involved are well described but the volume sensing mechanism which can sense 2-3% changes in cell volume is not yet identified. Mechanisms shown to play a role in volume sensing include sensing of changes in membrane tension, and sensing of ionic-strength-mediated changes in protein-lipid interactions in the membrane bilayer. With respect to a role for membrane tension in volume sensing, it may be noted that given the large “excess membrane surface” found in most cell types in form of membrane invaginations, the cell membrane is likely to be unfolded rather than stretched after cell swelling, and volume-dependent changes in membrane tension may be of little importance in cell volume sensing whereas changes in membrane curvature could be of importance. There is also evidence specifically pointing to a role for the lipid bilayer in volume sensing. Changes in membrane cholesterol content have been found to modulate the function of a variety of membrane transporters and channels and decreases in membrane cholesterol content stimulate the swelling activate Chloride channel or make it more sensitive to minor cell swelling in several cell types suggesting that it modulates the volume-sensing mechanism. The modulation by cholesterol is proposed somehow to involve a change in the physical properties of the membrane. Moreover, cholesterol modulates membrane deformation energy which seems to be important for channel opening. In addition we find in Ehrlich Ascites tumour cells that an increase in the membrane content of polyunsaturated fatty acids which decreases the membrane deformation energy increased the swelling activated Cl- permeability and the rate of volume regulation. Thus central findings concerning the common upstream elements of volume sensing and volume-sensitive signal transduction events points to the lipid bilayer itself as a sensor.