Naegleria’s mitotic spindles are built from unique tubulins and highlight core spindle features

Kennard, Andrew S.; Trupinić, Monika; Ivec, Arian; Swafford, Austin D.; Nolton, Emily; Rice, Luke M.; Tolić, Iva Marija; Fritz‐Laylin, Lillian K.; Wadsworth, Patricia

doi:10.1016/j.cub.2022.01.034

Cited by 18 publications

(27 citation statements)

References 88 publications

(170 reference statements)

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“…A preliminary paper extends the result of the Lee laboratory on strain NB-1 α6 tubulin ( Velle et al, 2022 ). Both putative mitotic α-tubulin genes of strain N. gruberi NEG-M are shown to be expressed in growing amoebae, and this finding is extended to both putative mitotic β -tubulin genes of NEG-M, with none of the four genes expressed during differentiation.…”

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

confidence: 67%

“…In mitotic Naegleria , the microtubules appear quite normal at electron microscope resolution ( Fulton, 1970 , Figure 11; Schuster, 1975 ). Walsh has published a magisterial study of mitosis ( Walsh, 2012 ), to which ( Velle et al, 2022 ) offer some helpful additions. Nothing known about mitosis suggests that its tubulin would be “abnormal.” Unusually in Naegleria the nucleolus does not disassemble during mitosis, but divides with the chromosomes ( Walsh, 2012 ).…”

Section: How Naegleria Led Us To the Multi-tubulin...mentioning

confidence: 99%

“…So far the divergent putative mitotic tubulins have only been found within the few sequenced Heterolobosea ( Velle et al, 2022 ). Now that the N. fowleri genome has been expanded ( Liechti et al, 2019 ), when one searches databases using the putative mitotic tubulins from N. gruberi , one finds similar, but somewhat divergent, homologous pairs in the N. fowleri genome, as well as homologs to both flagellar tubulin subunits.…”

Section: What We Have Learned About the Unanticipated Diversity Of Eu...mentioning

confidence: 99%

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

confidence: 67%

Section: How Naegleria Led Us To the Multi-tubulin...mentioning

confidence: 99%

Section: What We Have Learned About the Unanticipated Diversity Of Eu...mentioning

confidence: 99%

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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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“…In contrast to the left-handed twist of human spindles, spindles in the amoeba Naegleria gruberi are twisted in a right-handed fashion 30 , which may be due to the differences in kinesins and other microtubule-associated proteins between Naegleria and humans. Naegleria lacks homologs to subunits of the augmin complex 69 , which is in line with the right-handed twist of spindles in this amoeba and in RPE1 cells depleted of augmin.…”

Section: Mechanisms That Generate Spindle Twistmentioning

confidence: 87%

“…Another organism whose spindles are prominently twisted is a unicellular eukaryote, amoeba Naegleria gruberi . Interestingly, amoeba’s spindles are predominantly twisted in a right-handed fashion 30 .…”

Section: Introductionmentioning

confidence: 99%

The chirality of the mitotic spindle provides a mechanical response to forces and depends on microtubule motors and augmin

Trupinić

Kokanović

Ponjavić

et al. 2020

Preprint

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Mechanical forces produced by motor proteins and microtubule dynamics within the mitotic spindle are crucial for the movement of chromosomes and their segregation into the emerging daughter cells. In addition to linear forces, rotational forces are present in the spindle, reflected in the left-handed twisted shapes of microtubule bundles that make the spindle chiral. However, the molecular origins of spindle chirality are unknown. Here we show that spindles are most twisted at the beginning of anaphase, and reveal multiple molecular players involved in spindle chirality. Inhibition of Eg5/kinesin-5 in a non-cancer cell line abolished spindle twist and depletion of Kif18A/kinesin-8 resulted in a right-handed twist, implying that these motors regulate twist likely by rotating the microtubules around one another within the antiparallel overlaps of bridging fibers. Depletion of the crosslinker PRC1 resulted in a right-handed twist, indicating that PRC1 may contribute to the twist by constraining free rotation of microtubules. Overexpression of PRC1 abolished twist, possibly due to increased torsional rigidity of the bundles. Depletion of augmin led to a right-handed twist, suggesting that twist depends on the geometry of microtubule nucleation. Round spindles were more twisted than elongated ones, a notion that we directly tested by compressing the spindle along its axis, which resulted in stronger left-handed twist, indicating a correlation between bending moments and twist. We conclude that spindle twist is controlled by multiple molecular mechanisms acting at different locations within the spindle as well as forces, and propose a potential physiological role of twist in promoting passive mechanical response of the spindle to forces during metaphase.

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Cell polarity in the protist-to-animal transition

Brunet¹,

Booth²

2023

Current Topics in Developmental Biology

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Naegleria’s mitotic spindles are built from unique tubulins and highlight core spindle features

Cited by 18 publications

References 88 publications

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

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

The chirality of the mitotic spindle provides a mechanical response to forces and depends on microtubule motors and augmin

Cell polarity in the protist-to-animal transition

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