Membrane Thickness as a Key Factor Contributing to the Activation of Osmosensors and Essential Ras Signaling Pathways

Abstract

The cell membrane provides a functional link between the external environment and the replicating DNA genome by using ligand-gated receptors and chemical signals to activate signaling transduction pathways. However, increasing evidence has also indicated that the phospholipid bilayer itself by altering various physical parameters serves as a sensor that regulate membrane proteins in a specific manner. Changes in thickness and/or curvature of the membrane have been shown to be induced by mechanical forces and transmitted through the transmembrane helices of several types of mechanosensitive (MS) ion channels underlying functions such as osmoregulation in bacteria and sensory processing in mammalian cells. This review focus on recent protein functional and structural data indicating that the activation of bacterial and yeast osmosensors is consistent with thickness-induced tilting changes of the transmembrane domains of these proteins. Membrane thinning in combination with curvature changes may also lead to the lateral transfer of the small lipid-anchored GTPases Ras1 and H-Ras out of lipid rafts for clustering and signaling. The modulation of signaling pathways by amphiphilic peptides and the membrane-active antibiotics colistin and Amphotericin B is also discussed.

From Pinocytosis to Methuosis—Fluid Consumption as a Risk Factor for Cell Death

“…Activation occurs once the lipid-anchored GTPases Ras1 and H-Ras are shifted out of the lipid rafts. This happens upon thinning of the PM in combination with changes of its curvature induced by cell swelling ( Cohen, 2018 ).…”

Spatiotemporal Regulation of Signaling: Focus on T Cell Activation and the Immunological Synapse

“…Mechanical forces spread across the plasma membrane via a range of systems including integrins and adhesion proteins in conjunction with the actin cytoskeleton, mechanosensitive receptors, and mechanosensitive ion channels. Transmission of these forces greatly depends on the biophysical properties of the plasma membrane including pH, electrostatic charges, membrane thickness, membrane fluidity, and membrane tension as well as on the properties of the stimuli [28][29][30]. For instance, mechanosensitive ion channels participate in regulating cell volume by sensing and responding to changes in tension and stretching of the plasma membrane, being directly linked to membrane elasticity and external stiffness (from either an interacting cell or from the extracellular matrix) [31].…”

The Plasma Membrane—An Integrating Compartment for Mechano-Signaling

“…Indeed, it is already well known in bacteria and yeast that the activation of osmosensors is correlated with thickness-induced conformational changes in the transmembrane domains of those sensors. For example, antimicrobial peptides cause thinning effects of the plasma membrane leading to changes of the transmembrane domain of PhoQ, a bacterial histidine kinase, resulting in the phosphorylation and subsequent activation of the kinase (reviewed in [34]). So far, there is no similar mechanism described in plants.…”