Department of Cell and Developmental Biology, University of Colorado School of Medicine , Aurora, CO, USA.
J Cell Biol. 2023 Mar 6;222(3). doi: 10.1083/jcb.202202102. Epub 2023 Jan 31.
How cells regulate α- and β-tubulin to meet the demand for αβ-heterodimers and avoid consequences of monomer imbalance is not understood. We investigate the role of gene copy number and how shifting expression of α- or β-tubulin genes impacts tubulin proteostasis and microtubule function in Saccharomyces cerevisiae. We find that α-tubulin gene copy number is important for maintaining excess α-tubulin protein compared to β-tubulin protein. Excess α-tubulin prevents accumulation of super-stoichiometric β-tubulin, which leads to loss of microtubules, formation of non-microtubule assemblies of tubulin, and disrupts cell proliferation. In contrast, sub-stoichiometric β-tubulin or overexpression of α-tubulin has minor effects. We provide evidence that yeast cells equilibrate α-tubulin protein concentration when α-tubulin isotype expression is increased. We propose an asymmetric relationship between α- and β-tubulins, in which α-tubulins are maintained in excess to supply αβ-heterodimers and limit the accumulation of β-tubulin monomers.
细胞如何调节α-和β-微管蛋白以满足αβ-异二聚体的需求并避免单体失衡的后果尚不清楚。我们研究了基因拷贝数的作用，以及α-或β-微管蛋白基因表达的变化如何影响酿酒酵母中的微管蛋白稳态和微管功能。我们发现，与β-微管蛋白相比，α-微管蛋白基因拷贝数对于维持过量的α-微管蛋白至关重要。过量的α-微管蛋白可防止超化学计量的β-微管蛋白积累，从而导致微管丢失、微管蛋白形成非微管组装体，并破坏细胞增殖。相比之下，β-微管蛋白亚化学计量或α-微管蛋白过表达的影响较小。我们提供的证据表明，当增加α-微管蛋白同工型表达时，酵母细胞会平衡α-微管蛋白蛋白浓度。我们提出了α-和β-微管蛋白之间的不对称关系，其中α-微管蛋白保持过量以供应αβ-异二聚体并限制β-微管蛋白单体的积累。
