Detailseite
Projekt
Regulation of ciliogenesis and ciliary disassembly by nephrocystins
Antragsteller
Professor Dr. Manfred Jung; Professor Dr. Gerd Walz
Fachliche Zuordnung
Nephrologie
Förderung
Förderung von 2008 bis 2015
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 58488057
Nephronophthisis is an autosomal recessive cystic kidney disease caused by mutations of nephrocystins. Preliminary results revealed that three nephrocystins (NPHP1, 2, 4) regulate the activity of Hef1/Aurora A, a complex that triggers ciliary disassembly through activation of histone deacytelases (HDACs). Since HDAC inhibitors rescue the ciliogenesis defect induced by the loss of NPHP2/lnversin, these findings suggest that some nephrocystins control the balance between ciliary assembly and disassembly. This project will therefore focus on the role of nephrocystins in the regulation of ciliogenesis and ciliary disassembly. The specific aims will 1) elucidate the mechanisms through which nephrocystins regulate ciliogenesis and ciliary disassembly, 2) test which ciliary defects are sensitive to HDACi, and 3) establish an in vitro model to screen for compounds that facilitate ciliogenesis, and exploit the potential of HDACi to suppress cyst formation in animal models of polycystic kidney disease.
DFG-Verfahren
Klinische Forschungsgruppen
