GENETIC AND PHYSICAL INTERACTIONS BETWEEN SRP1P AND NUCLEAR-PORE COMPLEX PROTEINS NUP1P AND NUP2P

Nup1p is a yeast nuclear pore complex protein (nucleoporin) required f or nuclear protein import, mRNA export and maintenance of normal nucle ar architecture. We have used a genetic approach to identify other pro teins that interact functionally with Nup1p. Here we describe the isol ation of seventeen mutants that confer a requirement for Nup1p in a ba ckground in which this protein is normally not essential. Some of the mutants require wild-type Nup1p, while others are viable in combinatio n with specific nup1 alleles. Several of the mutants show nonallelic n oncomplementation, suggesting that the products may be part of a heter o-oligomeric complex. One is allelic to srp1 which, although it was id entified in an unrelated screen, was shown to encode a protein that is localized to the nuclear envelope (Yano, R., M. Oakes, M. Yamaghishi, J. A. Dodd, and M. Nomura. 1992. Mol. Cell. Biol. 12:5640-5651). We h ave used immunoprecipitation and fusion protein precipitation to show that Srp1p forms distinct complexes with both Nup1p and the related nu cleoporin Nup2p, indicating that Srp1p is a component of the nuclear p ore complex. The distant sequence similarity between Srp1p and the bet a-catenin/desmoplakin family, coupled with the altered structure of th e nuclear envelope in nup1 mutants, suggests that Srp1p may function i n attachment of the nuclear pore complex to an underlying nuclear skel eton.