Activation of kinases upon volume changes: role in cellular homeostasis

Abstract

The cell is constantly encountering stimuli or conditions that can induce alterations to cell volume. Despite these challenges, cell volume remains relatively constant, by virtue of a series of complex and often redundant regulatory mechanisms. Acutely, an efflux of ions and organic osmolytes counteracts the tendency of cells to swell. Conversely when cells are exposed to perturbations that cause shrinkage, ions are rapidly imported. Chronic hypertonic stimulation increases the transcription of multiple genes whose products promote the intracellular accumulation of organic osmolytes. How the cell perceives these acute alterations in volume in order to signal the activation of specific channels, transporters and transcription factors has been the focus of a large body of research. In this article, we describe the central role that kinases play in mediating the cellular responses to alterations in cell volume. Although incompletely understood, these fundamental processes are key to cellular homeostasis and have obvious clinical implications.