Protein/protein interactions (PDZ) in proximal tubules

Using kidney cDNA libraries and single proximal tubular proteins as baits, the yeast two-hybrid technology resulted in the description of numerous potential PDZ-based protein-protein interactions. Many of these have been confirmed by biochemical in-vitro assays. In order to assign cellular functions of such proteins, it is first mandatory to define the precise distribution and localization in PT cells of each canditate protein. This prerequisite has been assessed only for a few of the PDZ proteins mentioned in this article. In addition, it remains to be deciphered how the interactions of the identified PDZ proteins are modulated, for example, by phosphorylation reactions or by other posttranslational modifications. As mentioned in this article, PDZ knock-out mouse models may be of help to elucidate the physiological and pathophysiological functions of a particular PDZ interaction. However, current data indicate that, despite the robust interactions observed in in-vitro assays, ablation of a certain PDZ protein does not necessarily result in an expected phenotype, probably due to functional compensation by other PDZ proteins. Therefore, it has to be assumed that a large redundancy of known and as yet unidentified PDZ proteins exists in proximal tubular cells. © Springer Science+Business Media, Inc. 2005.