Identification of binding partners and regulatory mechanism (Abstract)
Autosomal Dominant Tubulointerstitial Kidney Disease (ADTKD) are rare monogenetic diseases of the kidney, which are mainly caused by germline mutations of UMOD and MUC1. The latter arises by abnormal storage in COPI/II vesicles of an exclusive frameshifted protein (MUC1-fs) between the endoplasmic reticulum and the Golgi apparatus.
In the COPI/II vesicles MUC1-fs appears to be trapped tot he cargo receptor „transmembrane emp24 domain 9“ protein (TMED9) leading to cytoplasmic accumulation of the protein. Pharmacological downregulation of TMED9 releases MUC1-fs to lysosomal degradation. However, pathophysiological mechanisms of cellular damage by vesicular storage of MUC1-fs are incompletely understood. Therefore, this project aims to identify protein binding partners of MUC1-fs in renal tubular cells. Furthermore, it aims to characterize cellular distribution and regulation of TMED9.
In concert, these data should enhance our knowledge on the pathomechanism of ADTKD-MUC1, which will be important in tailoring specific means of therapeutical intervention.