THE CALNEXIN HOMOLOG CNX1(-POMBE, IS AN ESSENTIAL GENE WHICH CAN BE COMPLEMENTED BY ITS SOLUBLE ER DOMAIN() IN SCHIZOSACCHAROMYCES)

Secretory proteins become folded by the action of a number of molecula r chaperones soon after they enter the endoplasmic reticulum (ER). In mammalian cells, the ER membrane protein calnexin has been shown to be a molecular chaperone involved in the folding of secretory proteins a nd in the assembly of cell surface receptor complexes. We have used a PCR strategy to identify the Schizosaccharomyces pombe calnexin homolo gue, cnx1(+). The cnx1(+) encoded protein, Cnx1, was shown to be a cal cium binding type I integral membrane glycoprotein. At its 5' end, the cnx1(+) gene has consensus heat shock transcriptional control element s and was inducible by heat shock and by the calcium ionophore A23187. Unlike the sequence-related Saccharomyces cerevisiae CNE1 gene, the S .pombe cnx1(+) gene was essential for cell viability. The full-length Cnx1 protein was able to complement the cnx1(+) gene disruption but th e full-length mammalian calnexin could not. The ER lumenal domain of C nx1, which was secreted from cells, was capable of complementing the c nx1::ura4 lethal phenotype. The equivalent region of mammalian calnexi n has been shown to possess molecular chaperone activity. It is possib le that the lethal phenotype is caused by the absence of this chaperon e activity in the S.pombe cnx1(+) gene disruption.