Effect of tubulin self-association on GTP hydrolysis and nucleotide exchange reactions

Shemesh, Asaf; Ghareeb, Hiba; Dharan, Raviv; Levi‐Kalisman, Yael; Metanis, Norman; Ringel, Israel; Raviv, Uri

doi:10.1016/j.bbapap.2022.140869

Cited by 5 publications

(3 citation statements)

References 82 publications

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“…Another aspect of spindle assembly that could be susceptible to altered energy homeostasis is the requirement for guanosine triphosphate (GTP) in spindle assembly during meiosis (Cesario and McKim, 2011, Drutovic et al, 2020, Caplow and Shanks, 1990, Shemesh et al, 2023. The energy required for spindles to physically pull sister chromatids in opposing directions is derived from the lattice energy that is stored in tubulin microtubules (Caplow et al, 1994, Vulevic andCorreia, 1997), whose initial assembly is fuelled by the hydrolysis of GTP by Ras-related nuclear protein (Ran-GTP) Shanks, 1990, Shemesh et al, 2023).…”

Section: Oocyte Mitochondria and Atp Generationmentioning

confidence: 99%

Reproductive Ageing: Metabolic contribution to age-related chromosome missegregation in mammalian oocytes

Mihalas,

Marston,

et al. 2024

Reproduction

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Advanced maternal age is a major cause of infertility, miscarriage, and congenital abnormalities. This is principally caused by a decrease in oocyte quality and developmental competence with age. Oocyte ageing is characterised by an increase in chromosome missegregation and aneuploidy. However, the underlying mechanisms of age-related aneuploidy have not been fully elucidated and are still under active investigation. In addition to chromosome missegregation, oocyte ageing is also accompanied by metabolic dysfunction. In this review, we integrate old and new perspectives on oocyte ageing, chromosome segregation and metabolism in mammalian oocytes and make direct links between these processes. We consider age-related alterations to chromosome segregation machinery, including the loss of cohesion, microtubule stability and the integrity of the spindle assembly checkpoint. We focus on how metabolic dysfunction in the ageing oocyte disrupts chromosome segregation machinery to contribute to and exacerbate age-related aneuploidy. More specifically, we discuss how mitochondrial function, ATP production and the generation of free radicals are altered during ageing. We also explore recent developments in oocyte metabolic ageing, including altered redox reactions (NAD+ metabolism) and the interactions between oocytes and their somatic nurse cells. Throughout the review we integrate the mechanisms by which changes in oocyte metabolism influence age-related chromosome missegregation.

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Section: Oocyte Mitochondria and Atp Generationmentioning

confidence: 99%

Reproductive Ageing: Metabolic contribution to age-related chromosome missegregation in mammalian oocytes

Mihalas,

Marston,

et al. 2024

Reproduction

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“…2 A). Inhibition of GTPase promotes polymerization of tubulin, a type of cytoskeleton [ 21 , 91 – 93 ] (Fig. 2 A).…”

Section: Effects Of CL − On Cytoskeletal Tubulin P...mentioning

confidence: 99%

Physiological roles of chloride ions in bodily and cellular functions

Marunaka

2023

J Physiol Sci

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Physiological roles of Cl−, a major anion in the body, are not well known compared with those of cations. This review article introduces: (1) roles of Cl− in bodily and cellular functions; (2) the range of cytosolic Cl− concentration ([Cl−]c); (3) whether [Cl−]c could change with cell volume change under an isosmotic condition; (4) whether [Cl−]c could change under conditions where multiple Cl− transporters and channels contribute to Cl− influx and efflux in an isosmotic state; (5) whether the change in [Cl−]c could be large enough to act as signals; (6) effects of Cl− on cytoskeletal tubulin polymerization through inhibition of GTPase activity and tubulin polymerization-dependent biological activity; (7) roles of cytosolic Cl− in cell proliferation; (8) Cl−-regulatory mechanisms of ciliary motility; (9) roles of Cl− in sweet/umami taste receptors; (10) Cl−-regulatory mechanisms of with-no-lysine kinase (WNK); (11) roles of Cl− in regulation of epithelial Na+ transport; (12) relationship between roles of Cl− and H+ in body functions.

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“…Tubulin heterodimers with GTP-bound β-tubulin (hereinafter referred to as GTP-tubulin) polymerize into microtubules (Desai and Mitchison, 1997). As the microtubule elongates, longitudinal and lateral interactions of incorporated tubulin dimers activate β-tubulin GTPase activity, stochastically hydrolyzing the bound GTP and forming GDP-tubulin in the microtubule lattice (Shemesh et al, 2023;Nogales et al, 1998a). As a result, the growing ends of microtubules contain GTP-tubulin, called the GTP cap.…”

Section: Introductionmentioning

confidence: 99%

A tubulin-binding protein that preferentially binds to GDP-tubulin and promotes GTP exchange

Yon,

Ha,

Zheng

et al. 2023

Preprint

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α- and β-tubulin form heterodimers, with GTPase activity, that assemble into microtubules. Like other GTPases, the nucleotide-bound state of tubulin heterodimers controls whether the molecules are in a biologically active or inactive state. While α-tubulin in the heterodimer is constitutively bound to GTP, β-tubulin can be bound to either GDP (GDP-tubulin) or GTP (GTP-tubulin). GTP-tubulin hydrolyzes its GTP to GDP following assembly into a microtubule and, upon disassembly, must exchange its bound GDP for GTP to participate in subsequent microtubule polymerization. Tubulin dimers have been shown to exhibit rapid intrinsic nucleotide exchange in vitro, leading to a commonly accepted belief that a tubulin guanine nucleotide exchange factor (GEF) may be unnecessary in cells. Here, we use quantitative binding assays to show that BuGZ, a spindle assembly factor, binds tightly to GDP-tubulin, less tightly to GTP-tubulin, and weakly to microtubules. We further show that BuGZ promotes the incorporation of GTP into tubulin using a nucleotide exchange assay. The discovery of a tubulin GEF suggests a mechanism that may aid rapid microtubule assembly dynamics in cells.

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Effect of tubulin self-association on GTP hydrolysis and nucleotide exchange reactions

Cited by 5 publications

References 82 publications

Reproductive Ageing: Metabolic contribution to age-related chromosome missegregation in mammalian oocytes

Reproductive Ageing: Metabolic contribution to age-related chromosome missegregation in mammalian oocytes

Physiological roles of chloride ions in bodily and cellular functions

A tubulin-binding protein that preferentially binds to GDP-tubulin and promotes GTP exchange

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