ABSTRACT
The regulation of high osmolality is an important driving force for water reabsorption and urinary concentration--the key functions of the kidney for maintaining optimum body fluid volume. New evidence shows that transcription factor tonicity responsive enhancer binding protein (TonEBP) and calcineurin-nuclear factor of activated T cells through cross-talk enhance Aquaporin 2 (AQP2) expression. AQP2 is the predominant vasopressin regulated water channel of the kidney collecting duct and is essential for urinary concentration. The serine/threonine phosphatase calcineurin is an important signaling molecule involved in kidney development and function. One potential target of calcineurin action is the water channel AQP2. The nuclear factor of activated T cells (NFAT) family has recently been expanded by the discovery of a new member, NFAT 5, or Ton EBP. Ton EBP is the only known mammalian transcription factor that regulates gene expression in response to hypertonicity. This review examines the importance of AQP2, calcineurin, NFATc and TonEBP in the renal regulation of water homeostasis.