Project 1 - Functional characterization of intracellular sorting receptors in transepithelial transport processes in the kidney

Project Summary

Vps10p-domain receptors are a novel class of mammalian orphan receptors that exhibit structural similarity to endocytic and intracellular protein sorting receptors. Expression of Vps10p-domain receptors in epithelia of different nephron segments suggest a function for the proteins in transepithelial transport processes in the kidney. Aim of the project is the functional characterization of SorLA-1 and Sortilin, two members of the gene family in proximal tubule and in thick ascending limb of Henle’s loop that are implicated in intracellular transport of NKCC2 and other, so far unknown target proteins in the kidney. To do so, the role of SorLA-1 and Sortilin in the trafficking and activity of NKCC2 and other renal transporters will be analyzed in tissue culture and in transgenic animal models, including SorLA-1- and Sortilin-deficient mouse lines. Ultimately, our studies aim at a better understanding of the regulatory processes of ion handling in the kidney, as well as the pathological changes in patients with ion homeostasis and blood pressure disorders.

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