KAR5 ENCODES A NOVEL PHEROMONE-INDUCIBLE PROTEIN REQUIRED FOR HOMOTYPIC NUCLEAR-FUSION

KAR5 is required for membrane fusion during karyogamy, the process of nuclear fusion during yeast mating. To investigate the molecular mecha nism of nuclear fusion, we cloned and characterized the KAR5 gene and its product. KAR5 is a nonessential gene, and deletion mutations produ ce a bilateral defect in the homotypic fusion of yeast nuclei. KARS en codes a novel protein that shares similarity with a protein in Schizos accharomyces pombe that may play a similar role in nuclear fusion. Kar 5p is induced as part of the pheromone response pathway, suggesting th at this protein uniquely plays a specific role during mating in nuclea r membrane fusion. Kar5p is a membrane protein with its soluble domain entirely contained within the lumen of the endoplasmic reticulum. In pheromonetreated cells, Kar5p was localized to the vicinity of the spi ndle pole body, the initial site of fusion between haploid nuclei duri ng karyogamy. We propose that Kar5p is required for the completion of nuclear membrane fusion and may play a role in the organization of the membrane fusion complex.