Abstract
Changes in plasma membrane curvature and intracellular ionic strength are two key features of cell volume perturbations. In this hypothesis we present a model of the responsible molecular apparatus which is assembled of two molecular motors [non-muscle myosin II (NMMII) and protrusive actin polymerization], a spring [a complex between the plasma membrane (PM) and the submembrane actin-based cytoskeleton (smACSK) which behaves like a viscoelastic solid] and the associated signaling proteins. We hypothesize that this apparatus senses changes in both the plasma membrane curvature and the ionic strength and in turn activates signaling pathways responsible for regulatory volume increase (RVI) and regulatory volume decrease (RVD). During cell volume changes hydrostatic pressure (HP) changes drive alterations in the cell membrane curvature. HP difference has opposite directions in swelling versus shrinkage, thus allowing distinction between them. By analogy with actomyosin contractility that appears to sense stiffness of the extracellular matrix we propose that NMMII and actin polymerization can actively probe the transmembrane gradient in HP. Furthermore, NMMII and protein-protein interactions in the actin cortex are sensitive to ionic strength. Emerging data on direct binding to and regulating activities of transmembrane mechanosensors by NMMII and actin cortex provide routes for signal transduction from transmembrane mechanosensors to cell volume regulatory mechanisms.
Highlights
Cell fate and functioning, e.g., proliferation, migration, apoptosis, are accompanied and critically determined by appropriate changes in cell volume [1,2,3,4,5,6,7,8]
We propose that the pushing force generated by protrusive actin filaments [54] would probe the strength of HPout that drives the plasma membrane (PM)-submembrane actin-based cytoskeleton (smACSK) into the cell in case of cell shrinkage
We present an hypothesis that comprises four key features, (1) fine-tuning of cell volume set point (i.e., non-muscle myosin II (NMMII), F-actin protrusive activity and viscoelastic properties of PM-SMACSK complex) by cell fate, (2) probing of changes in difference in hydrostatic pressures (HPin versus HPout) across the PM by two active ATP-consuming mechanisms (NMMII and F-actin polymerization), (3) perfect elasticity of the PM-SMACSK complex, allowing its return to normal shape, and (4) sensing of changes in intracellular ionic strength by NMMII and machinery performing F-actin polymerization
Summary
E.g., proliferation, migration, apoptosis, are accompanied and critically determined by appropriate changes in cell volume [1,2,3,4,5,6,7,8]. Each heavy chain consists of 3 domains: the N-terminal globular head harboring the ATPase activity responsible for force generation and actin binding; the neck domain which binds to ELCs and RLCs, and the C-terminal α-helical rod domain with a nonhelical tail-piece needed for thick filament formation and cargo binding [16,17,18,19] This heterohexameric complex of 2 HCs, 2 ELCs and 2 RLCs is referred to as NMMII monomer, since it represents a functional unit, and NMMII monomers undergo assembly into filaments and stacks [19] (Figure 2). Phosphorylation/dephosphorylation of heavy chains of NMMII control behavior of NMMII [17]
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