Membranes Seminar

Please sign up for free lunch with the speaker after the seminar no later than 16 March at 12:00. 

Abstract

Calcium (Ca²⁺) balance is tightly regulated by the Ca²⁺-sensing receptor (CaSR) and Ca²⁺ sensing mechanisms in the kidney regulate Ca²⁺ excretion into urine. Elevated Ca²⁺ in urine (hypercalciuria) is the most common abnormality observed in kidney stone patients and the risk of stone formation and recurrence can be reduced by decreasing the urinary Ca²⁺ excretion. The CaSR is highly expressed in select renal epithelial cells where it functions to reduce Ca²⁺ reabsorption, when Ca²⁺ levels in blood increases. We have detailed that in vivo activation of the CaSR leads to a pronounced increase in renal Claudin-14 (Cldn14) gene expression. Although Claudin-14 is a tight junction protein, it is not pore-forming, but functions instead to block paracellular reabsorption of Ca²⁺. As such, variants in the CLDN14 gene have been described to markedly increase the risk of developing hypercalciuria and kidney stone disease. We have investigated the localization and regulation of Claudin-14 in kidney and used it to gauge renal CaSR activity. Using mouse models of CaSR activation to mimic the phenotype of patients with autosomal dominant hypocalcemia (ADH1) due to gain-of-function CaSR mutations, we have found CaSR activation in kidney occurs differently than previously thought and detailed how it contributes to this condition. Furthermore, we have utilized our transgenic systems to map how drugs assumed to exert their calciuretic effects by primarily affecting CaSR signaling in kidney, impact renal Ca²⁺ transport processes.  

On behalf of the organizer
Søren Brandt Poulsen
Administrative Research Theme Coordinator
MEMBRANES