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. Author manuscript; available in PMC: 2015 Jul 1.
Published in final edited form as: Curr Opin Nephrol Hypertens. 2014 Jul;23(4):352–360. doi: 10.1097/01.mnh.0000447016.21228.e0

Figure 2.

Figure 2

Simplified schema of a renal tubular epithelial cell in the TAL illustrating the CaSR-NFATc1-microRNA-CLDN14 pathway. CaSR activity on the basolateral membrane determines intracellular calcium-signaling and calcineurin activity, thereby regulating NFATc1 via (de)phosphorylation. When NFATc1 is activated, it translocates to the nucleus and increases transcription of CLDN14-regulating microRNAs miR-9-1 and miR-374. These microRNAs decrease CLDN14 expression and thereby alter the cation permeability of the paracellular ion channel formed by the CLDN16/CLDN19 heterodimer complex. CaSR could regulate CLDN14 by additional mechanisms as well. Abbreviations: CaSR = calcium-sensing receptor, NFATc1 = Nuclear Factor of Activated T-cells, cytoplasmic 1, CLDN = claudin, TAL = thick ascending limb