FIGURE 7.

Mechanism of intercalated cell (IC) mineralocorticoid receptor (MR) activation. When the IC MR is phosphorylated at S843, aldosterone binding to the MR is inhibited. However, angiotensin II acts through the angiotensin type 1 receptor (AT1R) and mammalian target of rapamycin (mTOR) to phosphorylate, and thereby inactivate, ULK1, a kinase that mediates MR S843 phosphorylation. By inhibiting ULK1, S843 phosphorylation does not occur, which facilitates aldosterone binding to and thus activation of the IC MR. Upon aldosterone binding, the IC MR is translocated to the nucleus, which promotes transcription of IC transporters such as pendrin.