PIGEA-14, a Novel Coiled-coil Protein Affecting the Intracellular Distribution of Polycystin-2

Employing a yeast two-hybrid screen with the COOH terminus of polycystin-2, one of the proteins mutated in patients with polycystic kidney disease, we were able to isolate a novel protein that we call PIGEA-14 ( p olycystin-2 i nteractor, G olgi- and e ndoplasmic reticulum- a ssociated protein with a molecular mass of 14 kDa). Molecular modeling only predicts a coiled-coil motif, but no other functional domains, in PIGEA-14. In a subsequent two-hybrid screen using PIGEA-14 as a bait, we found GM130, a component of the cis-compartment of the Golgi apparatus. Co-expression of the PIGEA-14 and PKD2 cDNAs in LLC-PK 1 and HeLa cells resulted in a redistribution of PIGEA-14 and polycystin-2 to the trans-Golgi network, which suggests that PIGEA-14 plays an important role in regulating the intracellular location of polycystin-2 and possibly other intracellular proteins. Our results also indicate that the intracellular trafficking of polycystin-2 is regulated both at the level of the endo-plasmic reticulum and that of the trans-Golgi network.