MODULATION OF TUBULIN POLYPEPTIDE RATIOS BY THE YEAST PROTEIN PAC10P

Normal assembly and function of microtubules require maintenance of th e proper levels of several proteins, including the tubulin polypeptide s themselves. For example, in yeast a significant excess of beta-tubul in causes rapid microtubule disassembly and subsequent cell death. Eve n the modest excess of beta-tubulin produced by genetic alterations su ch as deletion of the minor alpha-tubulin gene TUB3 affects cell growt h and can confer microtubule phenotypes. We show here that the levels of the yeast protein Pac10p affect the relative levels of the tubulin polypeptides. Cells deleted for PAC10 have the same phenotypes as do c ells that express reduced levels of alpha-tubulin or Rbl2p, two protei ns that bind beta-tubulin. Conversely, overexpression of Pac10p enhanc es the ability of alpha-tubulin or Rbl2p to suppress the lethality ass ociated with excess beta-tubulin. However, Pac10p is itself not a beta -tubulin binding protein. Pac10 null cells show a 30% decrease in the ratio of alpha-tubulin to beta-tubulin. The results suggest that Pac10 p modulates the level of alpha-tubulin in the cell, and so influences microtubule morphogenesis and tubulin metabolism.