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.
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6 March 2023
Article|
January 31 2023
Tubulin isotype regulation maintains asymmetric requirement for α-tubulin over β-tubulin
Linnea C. Wethekam
,
Linnea C. Wethekam
(Conceptualization, Formal analysis, Investigation, Methodology, Validation, Visualization, Writing - original draft, Writing - review & editing)
1
Department of Cell and Developmental Biology, University of Colorado School of Medicine
, Aurora, CO, USA
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Jeffrey K. Moore
(Conceptualization, Funding acquisition, Methodology, Project administration, Resources, Supervision, Visualization, Writing - original draft, Writing - review & editing)
1
Department of Cell and Developmental Biology, University of Colorado School of Medicine
, Aurora, CO, USA
Correspondence to Jeffrey K. Moore: Jeffrey.Moore@cuanschutz.edu
Search for other works by this author on:
Linnea C. Wethekam
Conceptualization, Formal analysis, Investigation, Methodology, Validation, Visualization, Writing - original draft, Writing - review & editing
1
Department of Cell and Developmental Biology, University of Colorado School of Medicine
, Aurora, CO, USA
Correspondence to Jeffrey K. Moore: Jeffrey.Moore@cuanschutz.edu
Disclosures: The authors declare no competing financial interests.
Received:
February 17 2022
Revision Received:
July 19 2022
Accepted:
November 14 2022
Online ISSN: 1540-8140
Print ISSN: 0021-9525
Funding
Funder(s):
National Institutes of Health
- Award Id(s): R01 GM112893,R35 GM 136253,T32 GM136444
Funder(s):
University of Colorado Molecular Biology Training Program
- Award Id(s): Bolie Scholar Award
© 2023 Wethekam and Moore
2023
Wethekam and Moore
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
J Cell Biol (2023) 222 (3): e202202102.
Article history
Received:
February 17 2022
Revision Received:
July 19 2022
Accepted:
November 14 2022
Citation
Linnea C. Wethekam, Jeffrey K. Moore; Tubulin isotype regulation maintains asymmetric requirement for α-tubulin over β-tubulin. J Cell Biol 6 March 2023; 222 (3): e202202102. doi: https://doi.org/10.1083/jcb.202202102
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