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Elucidation of the mechanism that keeps cell volume constant through the cooperative action of two proteins
Tomohiro Numata1 (Yasunobu Okada2)

The smallest unit that makes up our body, the cell, is kept at a constant volume even when exposed to excessive stimulation or abnormal environments. For example, when a cell loses its ability to regulate volume due to a viral infection, cell death and ultimately disease can ensue. Therefore, research on the underlying mechanisms as to how cell volume regulation leads to the control of cell life and death could in turn leads to the development of cell-based disease therapies.
Two channel proteins play essential roles in cell swelling: the swelling sensor protein (TRPM7 channel), and the protein that restores the original cell volume (VSOR Cl- channel). However, the relationship between these channels in suppressing cell swelling remained unclear.
Our research group focused on the control of cell volume when cells swell. Our results show that TRPM7 works in two ways. First, Ca2+ influx through TRPM7 augments mRNA expression of VSOR. Second, by stabilizing VSOR localization on the plasma membrane, TRPM7 promotes VSOR activity effectively reducing cell volume.
To our knowledge, this is the first study to report the mechanism by which two types of channel (TRPM7 and VSOR) proteins coordinate to regulate cell swelling, returning swollen cells to their original volume.

TRPM7 is an essential regulator for volume-sensitive outwardly rectifying anion channel.
Numata T, Sato-Numata K, Hermosura MC, Mori Y, Okada Y. Communications Biology 4(1): 599, 2021.

Functions of TRPM7 and VSOR that suppress swelling cell volume

1Department of Physiology, Graduate School of Medical Sciences, Fukuoka University, Japan.
2National Institute for Physiological Sciences, Japan.