Quantitative Regulation of Tubulin Expression

Pac10p is a subunit of the GimC/prefoldin complex that promotes folding of tubulin and other cytoskeletal proteins. Cells deleted for the PAC10 have excess undimerized beta-tubulin. Tubulin protein is down regulated in pac10D cells, -tubulin more than beta-tubulin, probably because the role of GimC/prefoldin is more important for beta-tubulin. As a result, pac10D cells have microtubule phenotypes and require both RBL2 and TUB3. Surprisingly, pac10D cells downregulate both a- and beta-tubulin mRNA levels. We are testing the hypothesis that the relationship between tubulin expression and a defect in protein folding represents feedback regulation of tubulin synthesis. Strains containing combinations of mutations that affect tubulin expression have only ~20% heterodimer levels compared to wild type cells. Nevertheless, these cells grow at rates comparable to wild type cells, but have altered spindle morphology and altered progress through mitosis. These cells provide a new opportunity to identify crucial effectors of microtubule formation and function.