Polycystin-1 interacts with intermediate filaments.

Polycystin-1, the protein defective in a majority of patients with autosoma l dominant polycystic kidney disease, is a ubiquitously expressed multi-spa n transmembrane protein of unknown function. Subcellular localization studi es found this protein to be a component of various cell junctional complexe s and to be associated with the cytoskeleton, but the specificity and natur e of such associations are not known. To identify proteins that interact wi th the polycystin-1 C-tail (P1CT), this segment was used as bait in a yeast two-hybrid screening of a kidney epithelial cell library. The intermediate filament (IF) protein vimentin was identified as a strong polycystin-1-int eracting partner. Cytokeratins K8 and K18 and desmin were also found to int eract with P1CT. These interactions were mediated by coiled-coil motifs in polycystin-1 and IF proteins. Vimentin, cytokeratins K8 and K18, and desmin also bound directly to P1CT in GST pull-down and in in vitro filament asse mbly assays. Two observations confirmed these interactions in vivo: (i) a c ell membrane-anchored form of recombinant P1CT decorated the IF network and was found to associate with the cytoskeleton in detergent-solubilized cell s and (ii) endogenous polycystin-1 distributed with IF at desmosomal juncti ons. Polycystin-1 may utilize this association for structural, storage, or signaling functions.