Tubulin isotypes optimize distinct spindle positioning mechanisms during yeast mitosis

Nsamba, Emmanuel T.; Bera, Abesh; Costanzo, Michael; Boone, Charles; Gupta, Mohan L.

doi:10.1083/jcb.202010155

Cited by 16 publications

(32 citation statements)

References 72 publications

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“…For example, the budding yeast Saccharomyces cerevisiae possesses two α-tubulin genes, TUB1 and TUB3, and a single β-tubulin gene, TUB2. The two α-tubulins generate approximately equal levels of mRNA, but different levels of soluble protein (Nsamba et al, 2021;Kilmartin and Adams, 1984;Gupta et al, 2002;Gartz Hanson et al, 2016;Barnes et al, 1992). This suggests that families of tubulin genes work additively to supply tubulin, but that the composition of the soluble tubulin pool must also be regulated by additional post-transcriptional mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Asymmetric requirement for α-tubulin over β-tubulin

Wethekam

Moore

2022

Preprint

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How cells regulate the supply of α- and β-tubulin monomers to meet the demand for αβ-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 α- or β-tubulin genes impacts tubulin proteostasis and microtubule function. We find that α-tubulin gene copy number is important for maintaining an excess α-tubulin protein compared to β-tubulin protein and preventing accumulation of super-stoichiometric β-tubulin. Super-stoichiometric β-tubulin is toxic to cells, leading to loss of microtubules, formation of non-microtubule assemblies of tubulin, and disrupted cell proliferation. In contrast, decreased β-tubulin or increased α-tubulin has minor effects. We provide evidence that cells rapidly equilibrate the concentration of α-tubulin protein during shifts in α-tubulin isotype expression to maintain a ratio in excess of β-tubulin. We propose an asymmetric relationship between α- and β-tubulins, where α-tubulins are maintained in excess to supply αβ-heterodimers and limit the accumulation of β-tubulin monomers.

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Section: Introductionmentioning

confidence: 99%

Asymmetric requirement for α-tubulin over β-tubulin

Wethekam

Moore

2022

Preprint

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“…due to relative expression levels (Schatz et al, 1986a). Subsequent studies supported the observation of more Tub1 relative to Tub3 in soluble protein extracts and purified tubulin (Bode et al, 2003;Hanson et al, 2016;Aiken et al, 2018), but it would be 35 years before a more detailed analysis of Tub1 and Tub3 function in vivo was reported (Nsamba et al, 2021).…”

Section: Saccharomyces Cerevisiaementioning

confidence: 96%

Microtubules in Microorganisms: How Tubulin Isotypes Contribute to Diverse Cytoskeletal Functions

Bera

Gupta

2022

Front. Cell Dev. Biol.

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The cellular functions of the microtubule (MT) cytoskeleton range from relatively simple to amazingly complex. Assembled from tubulin, a heterodimeric protein with α- and β-tubulin subunits, microtubules are long, hollow cylindrical filaments with inherent polarity. They are intrinsically dynamic polymers that utilize GTP binding by tubulin, and subsequent hydrolysis, to drive spontaneous assembly and disassembly. Early studies indicated that cellular MTs are composed of multiple variants, or isotypes, of α- and β-tubulins, and that these multi-isotype polymers are further diversified by a range of posttranslational modifications (PTMs) to tubulin. These findings support the multi-tubulin hypothesis whereby individual, or combinations of tubulin isotypes possess unique properties needed to support diverse MT structures and/or cellular processes. Beginning 40 years ago researchers have sought to address this hypothesis, and the role of tubulin isotypes, by exploiting experimentally accessible, genetically tractable and functionally conserved model systems. Among these systems, important insights have been gained from eukaryotic microbial models. In this review, we illustrate how using microorganisms yielded among the earliest evidence that tubulin isotypes harbor distinct properties, as well as recent insights as to how they facilitate specific cellular processes. Ongoing and future research in microorganisms will likely continue to reveal basic mechanisms for how tubulin isotypes facilitate MT functions, along with valuable perspectives on how they mediate the range of conserved and diverse processes observed across eukaryotic microbes.

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“…Lest we allow the ability of some organisms, such as the exampled yeast, to manage with single tubulin genes, to dull our sensitivity to tubulin isotypes, an elegant new paper shows a surprise: that while budding yeast can be engineered to grow with single α - and β -tubulin genes, both α-tubulin genes in a wildtype yeast are functional in spindle positioning ( Nsamba et al, 2021 ). As those studying tubulin isotypes have demonstrated repeatedly, there are subtleties in multiple tubulins.…”

Section: What We Have Learned About Naegleria ’S T...mentioning

confidence: 99%

The Amazing Evolutionary Complexity of Eukaryotic Tubulins: Lessons from Naegleria and the Multi-tubulin Hypothesis

Fulton

2022

Front. Cell Dev. Biol.

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The multi-tubulin hypothesis proposed in 1976 was motivated by finding that the tubulin to build the flagellar apparatus was synthesized de novo during the optional differentiation of Naegleria from walking amoebae to swimming flagellates. In the next decade, with the tools of cloning and sequencing, we were able to establish that the rate of flagellar tubulin synthesis in Naegleria is determined by the abundance of flagellar α- and β-tubulin mRNAs. These experiments also established that the tubulins for Naegleria mitosis were encoded by separate, divergent genes, candidates for which remain incompletely characterized. Meanwhile an unanticipated abundance of tubulin isotypes has been discovered by other researchers. Together with the surprises of genome complexity, these tubulin isotypes require us to rethink how we might utilize the opportunities and challenges offered by the evolutionary diversity of eukaryotes.

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Tubulin isotypes optimize distinct spindle positioning mechanisms during yeast mitosis

Cited by 16 publications

References 72 publications

Asymmetric requirement for α-tubulin over β-tubulin

Asymmetric requirement for α-tubulin over β-tubulin

Microtubules in Microorganisms: How Tubulin Isotypes Contribute to Diverse Cytoskeletal Functions

The Amazing Evolutionary Complexity of Eukaryotic Tubulins: Lessons from Naegleria and the Multi-tubulin Hypothesis

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