Self-repair promotes microtubule rescue

Aumeier, Charlotte; Schaedel, Laura; Gaillard, Jérémie; John, Karin; Blanchoin, Laurent; Théry, Manuel

doi:10.1038/ncb3406

Cited by 166 publications

(238 citation statements)

References 49 publications

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“…The cell’s careful control in defect removal suggests that defects impact microtubule-based processes. This is corroborated by a recent study that sheds new light on the biological effect of defects on the dynamic instability of microtubule growth30. Here, we seek to understand the effect of microtubule defects on motor-based intracellular transport.…”

mentioning

confidence: 61%

Single Molecule Investigation of Kinesin-1 Motility Using Engineered Microtubule Defects

Gramlich

Conway

Liang

et al. 2017

Sci Rep

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The structure of the microtubule is tightly regulated in cells via a number of microtubule associated proteins and enzymes. Microtubules accumulate structural defects during polymerization, and defect size can further increase under mechanical stresses. Intriguingly, microtubule defects have been shown to be targeted for removal via severing enzymes or self-repair. The cell’s control in defect removal suggests that defects can impact microtubule-based processes, including molecular motor-based intracellular transport. We previously demonstrated that microtubule defects influence cargo transport by multiple kinesin motors. However, mechanistic investigations of the observed effects remained challenging, since defects occur randomly during polymerization and are not directly observable in current motility assays. To overcome this challenge, we used end-to-end annealing to generate defects that are directly observable using standard epi-fluorescence microscopy. We demonstrate that the annealed sites recapitulate the effects of polymerization-derived defects on multiple-motor transport, and thus represent a simple and appropriate model for naturally-occurring defects. We found that single kinesins undergo premature dissociation, but not preferential pausing, at the annealed sites. Our findings provide the first mechanistic insight to how defects impact kinesin-based transport. Preferential dissociation on the single-molecule level has the potential to impair cargo delivery at locations of microtubule defect sites in vivo.

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mentioning

confidence: 61%

Single Molecule Investigation of Kinesin-1 Motility Using Engineered Microtubule Defects

Gramlich

Conway

Liang

et al. 2017

Sci Rep

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“…Because microtubules are very stiff polymers that rupture when subjected to flexural stresses (13), this highly bent morphology suggests the existence of protective mechanisms for long-lived microtubules. The repair of lattice defects has emerged as an intrinsic property of microtubules that are subjected to mechanical stress (14, 15) and acetylation protects microtubule from mechanical fatigue in vitro (4). Further suggesting that acetylation may confer mechanical protection to microtubules, removing TAT-1 from touch receptor neurons of nematodes results in profound microtubule lattice defects (6, 16) that can be rescued by paralyzing the animals (8).…”

Section: Main Textmentioning

confidence: 99%

Microtubules acquire resistance from mechanical breakage through intralumenal acetylation

Schaedel

Portran

et al. 2017

Science

Self Cite

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354

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Eukaryotic cells rely on long-lived microtubules for intracellular transport and as compression-bearing elements. Intriguingly, long-lived microtubules are acetylated inside their lumen and microtubule acetylation has been proposed to modify microtubule mechanics. Here we found that tubulin acetylation is required for the mechanical stabilization of long-lived microtubules in cells. Depletion of the tubulin acetyltransferase TAT1 led to a significant increase in the frequency of microtubule breakage and nocodazole-resistant microtubules lost upon removal of acetylation were largely restored by either pharmacological or physical removal of compressive forces. In vitro reconstitution experiments demonstrated that acetylation is sufficient to protect microtubules from mechanical breakage. Thus, acetylation increases mechanical resilience to ensure the persistence of long-lived microtubules.

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“…28, 29 When the free tubulin associates within the lattice defect, it is in the GTP form, in the straight conformation. 29 The healed site becomes mechanically and chemically more stable.…”

Section: Non-equilibrium Aspects Of the Assembly Of Tubulin Into Micrmentioning

confidence: 99%

“…28, 29 When the free tubulin associates within the lattice defect, it is in the GTP form, in the straight conformation. 29 The healed site becomes mechanically and chemically more stable. 28, 29 A recent cellular study has shown that the healing of microtubules enhances the mechanical stability in cells.…”

Section: Non-equilibrium Aspects Of the Assembly Of Tubulin Into Micrmentioning

confidence: 99%

Non-equilibrium assembly of microtubules: from molecules to autonomous chemical robots

2017

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Biological systems have evolved to harness non-equilibrium processes from the molecular to the macro scale. It is currently a grand challenge of chemistry, materials science, and engineering to understand and mimic biological systems that have the ability to autonomously sense stimuli, process these inputs, and respond by performing mechanical work. New chemical systems are responding to the challenge and form the basis for future responsive, adaptive, and active materials. In this article, we describe a particular biochemical-biomechanical network based on the microtubule cytoskeletal filament – itself a non-equilibrium chemical system. We trace the non-equilibrium aspects of the system from molecules to networks and describe how the cell uses this system to perform active work in essential processes. Finally, we discuss how microtubule-based engineered systems can serve as testbeds for autonomous chemical robots composed of biological and synthetic components.

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Self-repair promotes microtubule rescue

Cited by 166 publications

References 49 publications

Single Molecule Investigation of Kinesin-1 Motility Using Engineered Microtubule Defects

Single Molecule Investigation of Kinesin-1 Motility Using Engineered Microtubule Defects

Microtubules acquire resistance from mechanical breakage through intralumenal acetylation

Non-equilibrium assembly of microtubules: from molecules to autonomous chemical robots

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