Impact of the polycystins on establishment and maintenance of epithelial cell polarity

• Applicant: Privatdozent Dr. Bernd Dworniczak
• Subject Area: Cell Biology
• Term: from 2001 to 2007
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 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 Programme: Priority Programmes
• Subproject of: SPP 1111: Cell Polarity
• Participating Persons: Professor Dr. Jürgen Horst; Dr. Petra Pennekamp