Tubulin isotype regulation maintains asymmetric requirement for α-tubulin over β-tubulin

How cells regulate alpha- and beta-tubulin to meet the demand for alpha beta-heterodimers and avoid consequences of monomer imbalance is not understood. We investigate the role of gene copy number and how shifting expression of alpha- or beta-tubulin genes impacts tubulin proteostasis and microtubule function in Saccharomyces cerevisiae. We find that alpha-tubulin gene copy number is important for maintaining excess alpha-tubulin protein compared to beta-tubulin protein. Excess alpha-tubulin prevents accumulation of super-stoichiometric beta-tubulin, which leads to loss of microtubules, formation of non-microtubule assemblies of tubulin, and disrupts cell proliferation. In contrast, sub-stoichiometric beta-tubulin or overexpression of alpha-tubulin has minor effects. We provide evidence that yeast cells equilibrate alpha-tubulin protein concentration when alpha-tubulin isotype expression is increased. We propose an asymmetric relationship between alpha- and beta-tubulins, in which alpha-tubulins are maintained in excess to supply alpha beta-heterodimers and limit the accumulation of beta-tubulin monomers. Wethekam and Moore investigate how cells balance levels of alpha- and beta-tubulin to supply alpha beta-heterodimers. They found that cells produce higher levels of alpha-tubulin than beta-tubulin and require this excess to limit beta-tubulin accumulation. beta-tubulin accumulation causes microtubule loss and formation of dead-end tubulin assemblies.