Detailseite
Projekt
Impact of the polycystins on cilia function and establishment and maintenance of epithelial cell polarity
Antragsteller
Privatdozent Dr. Bernd Dworniczak
Fachliche Zuordnung
Zellbiologie
Förderung
Förderung von 2001 bis 2007
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 5333296
The establishment and maintenance of epithelial polarity is essential for the integrity and function of epithelial organs and is particularly critical in the kidney where directed reabsorption and secretion in different segments of the nephron is fundamental. Faulty or incomplete polarization of membranes cause serious disease. The best understood disease with manifest epithelial mispolarization is the autosomal dominant polycystic kidney disease (ADPKD), one of the most commonly inherited diseases in Caucasians. Mispolarization of epithelial cells cause the development and enlargement of multiple cysts within both kidneys which finally result in end-stage renal failure. By use of our Pkd2 knockout mouse - Pkd2 is one of the two genes mutated in ADPKD we will investigate the impact of the polycystins - the gene products of the Pkd genes which are thought to be involved in cell-cell or cell-matrix interactions - on establishment and maintenance of epithelial cell polarity. In vivo we will monitor progression of cellular polarization and depolarization during the development of the renal epithelia in polycystin 2 deficient kidneys. This will be complemented by in vitro experiments in polycystin-2 deficient renal epithelial cell lines aiming on the characterization of proteins known for both to influence cell polarity and to be influenced by or associated with one of the polycystins (E-cadherin, catenins, CD2AP, cytoskeletal proteins and others). Functional analysis and expression profiling by use of the GeneChip system in cultured cells will complete our analysis.
DFG-Verfahren
Schwerpunktprogramme
Teilprojekt zu
SPP 1111:
Zellpolarität
Beteiligte Personen
Professor Dr. Jürgen Horst; Dr. Petra Pennekamp
