Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent monogenic cause of kidney failure, characterized by the development of renal cysts. ADPKD is caused by mutations of the polycystin-1 (PC1) or polycystin-2 (PC2) genes. PC2 encodes a Ca 2؉ -permeable cation channel, and its dysfunction has been implicated in cyst development. The transcriptional coactivator with PDZ binding motif (TAZ) is required for the integrity of renal cilia. Its absence results in the development of renal cysts in a knock-out mouse model. TAZ directly interacts with PC2, and it has been suggested that another yet unidentified PDZ domain protein may be involved in the TAZ/PC2 interaction. Here we describe a novel interaction of TAZ with the multi-PDZ-containing PALS1-associated tight junction protein (PATJ). TAZ interacts with both the N-terminal PDZ domains 1-3 and the C-terminal PDZ domains 8 -10 of PATJ, suggesting two distinct TAZ binding domains. We also show that the C terminus of PC2 strongly interacts with PDZ domains 8 -10 and to a weaker extent with PDZ domains 1-3 of PATJ. Finally, we demonstrate that both TAZ and PATJ impair PC2 channel activity when co-expressed with PC2 in oocytes of Xenopus laevis. These results implicate TAZ and PATJ as novel regulatory elements of the PC2 channel and might thus be involved in ADPKD pathology.
EinleitungDer Ständige Ausschuss Reisemedizin (StAR) der Deutschen Gesellschaft für Tropenmedizin, Reisemedizin und Globale Gesundheit e. V. (DTG) erarbeitet jährlich Empfehlungen zu Reiseimpfungen und zur Malariaprophylaxe. Der StAR setzt sich aus Expertinnen und Experten der großen Tropeninstitute und tropenmedizinischen Abteilungen, des Auswärtigen Amts, der Bundeswehr, der Gesellschaft für Internationale Zusammenarbeit (GIZ), der Arbeitsmedizin, der Flugmedizin und maritimen Me-dizin, der Deutschen Gesellschaft für Reisemedizin (DFR) sowie des niedergelassenen Bereichs zusammen. Der StAR arbeitet eng mit dem schweizerischen Expertenkomitee für Reisemedizin (EKRM) zusammen. Ziel ist eine Harmonisierung der Malariaempfehlungen im deutschsprachigen Raum.Die im Folgenden zur besseren Lesbarkeit gewählte männliche Form bezieht sich immer zugleich auf weibliche, männliche und diverse Personen.
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