Impact of the ‘tubulin economy’ on the formation and function of the microtubule cytoskeleton

Ohi, Ryoma; Strothman, Claire E.; Žanić, Marija

doi:10.1016/j.ceb.2020.09.005

Cited by 21 publications

(13 citation statements)

References 76 publications

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“…This disparity is most likely due to the composite nature of the cytoskeleton, based around three protein filament networks with distinct structural, mechanical and biochemical properties: actin filaments, microtubules, and intermediate filaments ( Figures 1A,B ). All three filaments are reversible polymers that self-assemble from weakly interacting subunits whose local availability is a critical determinant of local cytoskeletal dynamics ( Plastino and Blanchoin 2018 ; Ohi et al, 2021 ). Both actin filaments and microtubules are structurally polar filaments, respectively composed of actin monomers that hydrolyze ATP, and tubulin dimers that hydrolyze GTP.…”

Section: Introductionmentioning

confidence: 99%

Intermediate Filaments in Cellular Mechanoresponsiveness: Mediating Cytoskeletal Crosstalk From Membrane to Nucleus and Back

Ndiaye

Koenderink

Shemesh

2022

Front. Cell Dev. Biol.

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The mammalian cytoskeleton forms a mechanical continuum that spans across the cell, connecting the cell surface to the nucleus via transmembrane protein complexes in the plasma and nuclear membranes. It transmits extracellular forces to the cell interior, providing mechanical cues that influence cellular decisions, but also actively generates intracellular forces, enabling the cell to probe and remodel its tissue microenvironment. Cells adapt their gene expression profile and morphology to external cues provided by the matrix and adjacent cells as well as to cell-intrinsic changes in cytoplasmic and nuclear volume. The cytoskeleton is a complex filamentous network of three interpenetrating structural proteins: actin, microtubules, and intermediate filaments. Traditionally the actin cytoskeleton is considered the main contributor to mechanosensitivity. This view is now shifting owing to the mounting evidence that the three cytoskeletal filaments have interdependent functions due to cytoskeletal crosstalk, with intermediate filaments taking a central role. In this Mini Review we discuss how cytoskeletal crosstalk confers mechanosensitivity to cells and tissues, with a particular focus on the role of intermediate filaments. We propose a view of the cytoskeleton as a composite structure, in which cytoskeletal crosstalk regulates the local stability and organization of all three filament families at the sub-cellular scale, cytoskeletal mechanics at the cellular scale, and cell adaptation to external cues at the tissue scale.

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Section: Introductionmentioning

confidence: 99%

Intermediate Filaments in Cellular Mechanoresponsiveness: Mediating Cytoskeletal Crosstalk From Membrane to Nucleus and Back

Ndiaye

Koenderink

Shemesh

2022

Front. Cell Dev. Biol.

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“… 47 , 48 , 49 It functions as establish and stabilize cell shape, maintains structural integrity, and participates in cell division, migration and other biological functions. 50 , 51 , 52 In the cell fate, cytoskeleton plays a vital role in the cell growth and development. It is well known that neural development is particularly reliant on functional microtubule structures.…”

Section: Discussionmentioning

confidence: 99%

Telomere shortening impairs alveolar regeneration

et al. 2022

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Objectives Short telomeres in alveolar type 2 (AT2) cells have been associated with many lung diseases. The study aimed to investigate the regeneration capacity of AT2 cells with short telomeres by knocking out Tert in mice (G4 Tert −/− ) from the whole to the cellular level. Materials and Methods The lung injury model of mice was established by left pneumonectomy (PNX). The proliferation and differentiation of AT2 cells were observed by immunofluorescence staining in vivo and in vitro. The difference of the gene expression between control and G4 Tert −/− group during the regeneration of AT2 cells was compared by RNA sequencing. The expression of tubulin polymerization promoting protein 3 (TPPP3) was reduced by adeno‐associated virus delivery. Results The alveolar regeneration in G4 Tert −/− mice was impaired after PNX‐induced lung injury. The regulation of cytoskeleton remodelling was defective in G4 Tert −/− AT2 cells. The expression of TPPP3 was gradually increased during AT2 cell differentiation. The expression level of TPPP3 was reduced in G4 Tert −/− AT2 cells. Reducing TPPP3 expression in AT2 cells limits the microtubule remodelling and differentiation of AT2 cells. Conclusion Short telomeres in AT2 cells result in the reduced expression level of TPPP3, leading to impaired regeneration capacity of AT2 cells.

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“…Efforts to understand microtubule growth have focused on the role of tubulin in the assembly of these cytoskeletal filaments, as the rate of assembly is typically proportional to the concentration of tubulin. Recently, a study summarized various ways by which the tubulin pool can affect microtubule nucleation, dynamics, and cytoskeletal organization (16). Notably, using FRET, it was shown that a local release of tubulin promoted microtubule extensions into lamellipodia, demonstrating a feedback between filament bound and soluble tubulin pools (17).…”

Section: Introductionmentioning

confidence: 99%

“…Free tubulin is known to affect microtubule dynamics by modulating rates of nucleation and polymerization (Geisterfer et al, 2020; King and Petry, 2020; Ohi et al, 2021; Woodruff et al, 2017). Notably, using FRET, it was shown that a local release of tubulin promoted microtubule extensions into lamellipodia, demonstrating a feedback between filament bound and free tubulin pools(Van Geel et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Ultrasensitivity of Microtubule severing rate on the concentration of free Tubulin

Shiff

Kondev

Mohapatra

2022

Preprint

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Cytoskeletal structures aid in cell polarization, motility, and intracellular transport. Their functions are predicated on the rapid turnover of cytoskeleton proteins, which is achieved by the coordinated effort of multiple regulatory proteins whose dynamics is not well understood. Recent in-vitro experiments have investigated mixtures of regulatory proteins and cytoskeletal filaments and have reported novel synergistic effects. For example, free tubulin can repair nanoscale damages of microtubules created by proteins that sever microtubules and, in doing so, affect their disassembly. Based on this observation, we propose a model for microtubule severing as a competition between the processes of damage spreading and tubulin-induced repair. Using theory and simulations, we demonstrate that this model is in quantitative agreement with in vitro experiments. We predict the existence of a critical tubulin concentration above which severing becomes rare but fast. Additionally, we find that microtubule length control via severing with tubulin-induced repair is hypersensitive to changes in the concentration of free tubulin and leads to a dramatically increased dynamic range of filament lengths in steady state. Our work describes how the concerted action of multiple microtubule associated proteins produces novel dynamical properties of these cytoskeletal filaments.Significance StatementHow cytoskeleton-associated proteins coordinate rapid turnover of cytoskeletal structures is not well understood. Recent experiments suggest that microtubule severing is the result of two competing processes of damage spreading and tubulin-induced repair. We find that this process predicts the existence of a critical tubulin concentration above which severing becomes rare but fast, and additionally, a dramatically increased dynamic range of microtubule filament lengths at steady state. This work describes how combining multiple microtubule associated proteins can produce novel dynamical properties which are not seen when these proteins are studied in isolation.

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Impact of the ‘tubulin economy’ on the formation and function of the microtubule cytoskeleton

Cited by 21 publications

References 76 publications

Intermediate Filaments in Cellular Mechanoresponsiveness: Mediating Cytoskeletal Crosstalk From Membrane to Nucleus and Back

Intermediate Filaments in Cellular Mechanoresponsiveness: Mediating Cytoskeletal Crosstalk From Membrane to Nucleus and Back

Telomere shortening impairs alveolar regeneration

Ultrasensitivity of Microtubule severing rate on the concentration of free Tubulin

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