THE YEAST NUCLEOPORIN NUP188P INTERACTS GENETICALLY AND PHYSICALLY WITH THE CORE STRUCTURES OF THE NUCLEAR-PORE COMPLEX

We have isolated a major protein constituent from a highly enriched fr action of yeast nuclear pore complexes (NPCs). The gene encoding this protein, Nup188p, was cloned, sequenced, and found to be nonessential upon deletion. Nup188p cofractionates with yeast NPCs and gives an imm unofluorescent staining pattern typical of nucleoporins. Using immunoe lectron microscopy, Nup188p was shown to localize to both the cytoplas mic and nucleoplasmic faces of the NPC core. There, Nup188p interacts with an integral protein of the pore membrane domain, Pom152p, and ano ther abundant nucleoporin, Nic96p. The effects of various mutations in the NUP188 gene on the structure of the nuclear envelope and the func tion of the NPC were examined. While null mutants of NUP188 appear nor mal, other mutants allelic to NUP188 exhibit a dominant effect leading to the formation of NPC-associated nuclear envelope herniations and g rowth inhibition at 37 degrees C. In addition, depletion of the intera cting protein Pom152p in cells lacking Nup188p resulted in severe defo rmations of the nuclear envelope. We suggest that Nup188p is one of a group of proteins that form the octagonal core structure of the NPC an d thus functions in the structural organization of the NPC and nuclear envelope.