INTERACTION OF BNR1P WITH A NOVEL SRC HOMOLOGY-3 DOMAIN-CONTAINING HOF1P - IMPLICATION IN CYTOKINESIS IN SACCHAROMYCES-CEREVISIAE

Proteins containing the formin homology (FH) domains FH1 and FH2 are i nvolved in cytokinesis or establishment of cell polarity in a variety of organisms. We have shown that the FH proteins Bni1p and Bnr1p are p otential targets of the Rho family small GTP-binding proteins and bind to an actin-binding protein, profilin, at their proline-rich FH1 doma ins to regulate reorganization of the actin cytoskeleton in the yeast Saccharomyces cerevisiae. We found here that a novel Src homology 3 (S H3) domain-containing protein, encoded by YMR032w, interacted with Bnr 1p in a GTP-Rho4p-dependent manner through the FH1 domain of Bnrlp and the SH3 domain of Ymr032wp. Ymr032wp weakly bound to Bni1p. Ymr032wp was homologous to cdc15p, which is involved in cytokinesis in Schizosa ccharomyces pombe, and we named this gene HOF1 (homolog of cdc 15). Bo th Bnrlp and Hof1p were localized at the bud neck, and both the bnr1 a nd hof1 mutations showed synthetic lethal interactions with the bni1 m utation. The hof1 mutant cells showed phenotypes similar to those of t he septin mutants, indicating that HOF1 is involved in cytokinesis. Th ese results indicate that Bnrlp directly interacts with Hof1p as well as with profilin to regulate cytoskeletal functions in S. cerevisiae.