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bioRxiv · 10.1101/2022.02.17.480930

Asymmetric requirement for α-tubulin over β-tubulin

Wethekam, L. C.·Moore, J. K.
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Abstract

How cells regulate the supply of - and {beta}-tubulin monomers to meet the demand for {beta}- heterodimers while avoiding consequences of monomer imbalance is not understood. We investigate the role of gene copy number in tubulin regulation and how shifting the expression of - or {beta}-tubulin genes impacts tubulin proteostasis and microtubule function. We find that - tubulin gene copy number is important for maintaining an excess -tubulin protein compared to {beta}-tubulin protein and preventing accumulation of super-stoichiometric {beta}-tubulin. Super- stoichiometric {beta}-tubulin is toxic to cells, leading to loss of microtubules, formation of non- microtubule assemblies of tubulin, and disrupted cell proliferation. In contrast, decreased {beta}- tubulin or increased -tubulin has minor effects. We provide evidence that cells rapidly equilibrate the concentration of -tubulin protein during shifts in -tubulin isotype expression to maintain a ratio in excess of {beta}-tubulin. We propose an asymmetric relationship between - and {beta}-tubulins, where -tubulins are maintained in excess to supply {beta}-heterodimers and limit the accumulation of {beta}-tubulin monomers.

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Wethekam, L. C., Moore, J. K.. 2022-02-19. Asymmetric requirement for α-tubulin over β-tubulin. https://doi.org/10.1101/2022.02.17.480930

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