Sensors and Signal Transduction Pathways in Vertebrate Cell Volume Regulation

Abstract

The ability to control cell volume is fundamental for proper cell function. This review highlights recent advances in the understanding of the complex sequences of events by which acute cell volume perturbation alters the activity of osmolyte transport proteins in cells from vertebrate organisms. After cell swelling, the main effectors in the process of regulatory volume decrease are swelling-activated K(+) and Cl(-) channels, a taurine efflux pathway, and KCl cotransport. After cell shrinkage, the main effectors in the process of regulatory volume increase are Na(+)/H(+) exchange, Na(+), K(+), 2Cl(-) cotransport, and in some cells, shrinkageactivated Na(+) channels. All of these proteins are regulated in a unique manner by cell volume perturbations. The molecular identity of most, although not all, of these transport pathways is now known. Among other important advances, this has lead to the identification of transporter binding partners such as protein kinases and phosphatases, cytoskeletal elements and lipids. Considerable progress has also been made recently in understanding the upstream elements in volume sensing and volume-sensitive signal transduction, and salient features of these systems will be discussed. In contrast to the simple pathway of osmosensing in yeast, cells from vertebrate organisms appear to exhibit multiple volume sensing systems, the specific mechanism(s) activated being cell type- and stimulus-dependent. Candidate sensors include integrins and growth factor receptors, while other early events include regulation of Rho family GTP binding proteins, Ste20-related protein kinases, and phospholipases, as well as cytoskeletal reorganization, Transient Receptor Potential channel-mediated Ca(2+) influx, and generation of reactive oxygen species.

Physiological and molecular mechanisms of salt and water homeostasis in the nematodeCaenorhabditis elegans

“…Ion and water transport mechanisms that compensate for changes in composition and volume of intracellular and extracellular compartments have been generally well defined using vertebrate cell and in vivo models (38). Alternatively, the upstream molecular mechanisms that animal cells use to sense deviations in salt and water balance and regulate compensatory responses are still poorly characterized (20).…”

Coordinated control of volume regulatory Na+/H+ and K+/H+ exchange pathways in Amphiuma red blood cells

“…ion transport; kinetics; erythrocytes; kinase; osmoregulation VOLUME ACTIVATED INORGANIC ion flux pathways that mediate cell volume regulation are well documented in a wide variety of cell types (for review, see Refs. 5,15,16,21,23,30) although the biochemical processes controlling the activity of these pathways are poorly understood (8,9,12,15,16,22,33). Kinetic manifestations of the volume-sensitive biochemical control processes have been described by several investigators (2, 10, 17-19, 24, 25, 27).…”

On the Role of G-Protein Coupled Receptors in Cell Volume Regulation

“…This reflects the importance for cell homeostasis of maintaining a strict volume control, including that of intracellular compartments, to preserve the cytoarchitecture required for the correct assembly of signaling complexes. Although systemic osmolarity in physiological conditions is highly controlled, intracellular osmolarity is continuously compromised by the generation of local and transient osmotic microgradients derived from 2 uptake of nutrients, secretion, synthesis and degradation of macromolecules, remodeling of the cytoskeleton and extracellular matrix and transynaptic ionic gradients [1,2]. Cell volume disturbances, particularly cell volume increase, occur in numerous pathologies.…”