Interplay between TonEBP and calcineurin-NFATc signaling pathways: a means of optimizing water reabsorption? Focus on “Calcineurin-NFATc signaling pathway regulates AQP2 expression in response to calcium signals and osmotic stress”

Abstract

CORRECT REGULATION of renal water reabsorption and urinary concentration is critical for the proper maintenance of body fluid volume. In comparison to the established role of the transcription factor tonicity-responsive enhancer binding protein (TonEBP) in the urinary concentration mechanism, that played by nuclear factor of activated T cells (NFAT) is less obvious. Now, Li et al. (6) provide evidence that links calcium signaling and water reabsorption by showing that transcription of the aquaporin (AQP)2 water channel is enhanced by the calcineurin-NFATc pathway. The authors show that while TonEBP and calcineurin-NFATc pathways each directly induce AQP2 transcription, cross talk occurring between both pathways further enhances AQP2 expression. The final checkpoint for renal water reabsorption occurs at the level of the collecting duct. High water permeability in this nephron segment is largely due to the presence of AQP2 inserted in the apical membrane of principal collecting duct cells. While the antidiuretic hormone (8-arginine)vasopressin (AVP) plays a major role in regulating AQP2 expression, several pieces of evidence indicate that this event is additionally influenced by hypertonicity (12). Water reabsorption increases along the osmotic gradient together with TonEBP expression. TonEBP is consequently highly expressed in the kidney medulla and the importance of TonEBP in renal physiology is well recognized. In contrast, while the calcineurinNFATc pathway has been extensively described in such di