What sets the TonE during osmotic stress?

Abstract

Cells are enclosed by a membrane that is readily penetrated by water but does not allow free diffusion of most solutes. Consequently, changes in external osmolality result in osmotic stress because of unequal rates of movement of water and solutes across the cell membrane. Cells respond to osmotic stress by osmoregulation, i.e., regulatory compensation of changes in cell volume, water content, and intracellular solute concentration. Osmoregulation minimizes changes in the concentration of intracellular inorganic ions—in particular Na+ and K+, macromolecules, and metabolites—and is essential for cell metabolism to operate properly. This is achieved by adjusting the levels of compatible osmolytes. Compatible osmolytes are small organic solutes, such as glycine betaine or myo-inositol, that are generally accumulated by transporters or enzymes, many of which are transcriptionally regulated. In this issue of the Proceedings, Miyakawa et al. (1) report the cloning and characterization of the first animal transcription factor responsible for regulating osmolyte transporter genes during osmotic stress. They name this transcription factor TonE binding protein (TonEBP) because it specifically binds to and activates the tonicity-responsive enhancer element (TonE) of osmoprotective genes, also known as osmotic response element. This important discovery should open up new avenues for addressing fundamental questions of cellular osmoregulation. In particular, it greatly contributes to understanding the molecular basis of osmosensory signal transduction.