GENETIC INTERACTIONS BETWEEN KAR2 AND SEC63, ENCODING EUKARYOTIC HOMOLOGS OF DNAK AND DNAJ IN THE ENDOPLASMIC-RETICULUM

KAR2 encodes the yeast homologue of mammalian BiP, the endoplasmic ret iculum (ER) resident member of the HSP70 family. Kar2p has been shown to be required for the translocation of proteins across the ER membran e as well as nuclear fusion. Sec63p, an ER integral membrane protein t hat shares homology with the Escherichia coli DnaJ protein, is also re quired for translocation. In this paper we describe several specific g enetic interactions between these two proteins, Kar2p and Sec63p. Firs t, temperature-sensitive mutations in KAR2 and SEC63 form synthetic le thal combinations. Second, dominant mutations in KAR2 are allele-speci fic suppressors for the temperature-sensitive growth and translocation defect of sec63-1. Third, the sec63-1, unlike other translocation def ective mutations, results in the induction of KAR2 mRNA levels. Taken together, these genetic interactions suggest that Kar2p and Sec63p int eract in vivo in a manner similar to that of the E. coli HSP70, DnaK, and DnaJ. We propose that the interaction between these two proteins i s critical to their function in protein translocation.