Analysis of the localization of STE6/CFTR chimeras in a Saccharomyces cerevisiae model for the cystic fibrosis defect CFTRΔF508

摘要: The use of yeast as a model system to study mammalian proteins is attractive, because genetic tools can be utilized if suitable phenotype created. STE6, the Saccharomyces cerevisiae a-factor mating pheromone transporter, and CFTR, cystic fibrosis transmembrane conductance regulator, are both members ATP binding cassette (ABC) superfamily. Teem et al. (1993) described for studying mutant form protein, CFTR delta F508. involved expression chimeric molecule in which portion STE6 was replaced with corresponding region from CFTR. STE6/CFTR chimera complemented ste6 strain mating, indicating that it could export a-factor. However, efficiency dramatically reduced upon introduction F508, providing this mutation. In human cells, F508 mutation results retention endoplasmic reticulum (ER), possibly reduction its chloride-channel activity. Here we examine basis differences activity promoted by wild-type chimeras. By analysis protein stability subcellular localization, find not ER-retained yeast. We conclude molecular must reflect capacity transport a-factor, rather than mistrafficking. Thus, appears good probe certain aspects function, but localization.