Emerging Roles of Monovalent Ion Transporters in Intracellular Signaling

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Background

This Research Topic of Frontiers in Physiology is dedicated to the memory of Dr. Sergei N. Orlov, who was the driving force behind this initiative but who unexpectedly passed away while working on the issue. Dr. Orlov was a pioneer and lifetime contributor to the field of pathophysiology of ion transport. In the early 1970’s, together with Yuvenali Postnov, he proposed the radical idea that the pathology of essential hypertension involves changes in activity of membrane monovalent ion transporters. This was just the beginning of his illustrious scientific career. During the last 20 years, he passionately explored the atypical mechanisms involved in the actions of cardiotonic steroids, signaling properties of intracellular sodium, and the enigmatic nature of sensors for intracellular monovalent ions.

The plasma membrane transport of monovalent ions – such as Na+, K+, and Cl- – sets and modulates transmembrane potential and cellular excitability, and fuels the secondary active accumulation of nutrients. Additionally, monovalent ion transporters and channels can impact cellular functions via activation of intracellular signaling processes. Traditionally, the “signaling” properties of monovalent ion transporters and channels have been ascribed to their indirect effects on intracellular Ca2+ levels.

However, emerging studies in the field point to many “atypical” roles for these membrane proteins and their roles in influencing cellular functions. The newly discovered signaling mechanisms include activation and modulation of cytosolic monovalent ion-sensing proteins and enzymes (e.g., Na+-sensitive GPCRs and the Cl--sensitive protein kinases from WNK family), formation of membrane scaffolds for intracellular signaling proteins, Ca2+-independent changes in gene expression, and initiation of atypical forms of cell death. The rapidly accumulating evidence for the signaling role of monovalent ions adds to and evolves our understanding of information transfer within and between animal cells.

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