Tubulin post‐translational modifications control neuronal development and functions

Moutin, Marie‐Jo; Bosc, Christophe; Peris, Leticia; Andrieux, Annie

doi:10.1002/dneu.22774

Cited by 71 publications

(72 citation statements)

References 197 publications

(276 reference statements)

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“…Post-translational modifications of tubulin—including tyrosination, polyamination, polyglutamylation, and acetylation—were shown to modulate MT stability by altering their dynamic properties (Moutin et al, 2020 ), resistance to cold exposure (Song et al, 2013 ), sensitivity to severing enzymes (Lacroix et al, 2010 ; Valenstein and Roll-Mecak, 2016 ), and flexibility (Portran et al, 2017 ; Xu et al, 2017 ). Finally, the so-called structural MAPs which bind throughout the MT lattice also influence MT stabilization.…”

Section: Introductionmentioning

confidence: 99%

Beyond Neuronal Microtubule Stabilization: MAP6 and CRMPS, Two Converging Stories

Cuveillier

Boulan

Ravanello

et al. 2021

Front. Mol. Neurosci.

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The development and function of the central nervous system rely on the microtubule (MT) and actin cytoskeletons and their respective effectors. Although the structural role of the cytoskeleton has long been acknowledged in neuronal morphology and activity, it was recently recognized to play the role of a signaling platform. Following this recognition, research into Microtubule Associated Proteins (MAPs) diversified. Indeed, historically, structural MAPs—including MAP1B, MAP2, Tau, and MAP6 (also known as STOP);—were identified and described as MT-binding and -stabilizing proteins. Extensive data obtained over the last 20 years indicated that these structural MAPs could also contribute to a variety of other molecular roles. Among multi-role MAPs, MAP6 provides a striking example illustrating the diverse molecular and cellular properties of MAPs and showing how their functional versatility contributes to the central nervous system. In this review, in addition to MAP6’s effect on microtubules, we describe its impact on the actin cytoskeleton, on neuroreceptor homeostasis, and its involvement in signaling pathways governing neuron development and maturation. We also discuss its roles in synaptic plasticity, brain connectivity, and cognitive abilities, as well as the potential relationships between the integrated brain functions of MAP6 and its molecular activities. In parallel, the Collapsin Response Mediator Proteins (CRMPs) are presented as examples of how other proteins, not initially identified as MAPs, fall into the broader MAP family. These proteins bind MTs as well as exhibiting molecular and cellular properties very similar to MAP6. Finally, we briefly summarize the multiple similarities between other classical structural MAPs and MAP6 or CRMPs.In summary, this review revisits the molecular properties and the cellular and neuronal roles of the classical MAPs, broadening our definition of what constitutes a MAP.

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Section: Introductionmentioning

confidence: 99%

Beyond Neuronal Microtubule Stabilization: MAP6 and CRMPS, Two Converging Stories

Cuveillier

Boulan

Ravanello

et al. 2021

Front. Mol. Neurosci.

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“…MT dynamics rely on the intrinsic capacity of MTs to alternate phases of polymerization and depolymerization. Various cellular factors have been shown to modulate MT dynamics including the nature of tubulin isoforms, GTP hydrolysis, MT associated proteins and also various post translational modifications (PTMs) of tubulin 18, 19 . One prominent modification is the reversible removal of the C-terminal tyrosine residue of α-tubulin subunits, which is exposed at the external surface of MTs.…”

Section: Introductionmentioning

confidence: 99%

Impaired α-tubulin re-tyrosination leads to synaptic dysfunction and is a feature of Alzheimer’s disease

Peris

Soleilhac

et al. 2021

Preprint

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In neurons, dynamic microtubules play regulatory roles in neurotransmission and synaptic plasticity. While stable microtubules contain detyrosinated tubulin, dynamic microtubules are composed of tyrosinated tubulin, suggesting that the tubulin tyrosination/detyrosination (Tyr/deTyr) cycle modulates microtubule dynamics and synaptic function. In the Tyr/deTyr cycle, the C-terminal tyrosine of alpha-tubulin is re-added by tubulin-tyrosine-ligase (TTL). Here we show that TTL+/- mice exhibit decreased tyrosinated microtubules, synaptic plasticity and memory deficits, and that reduced TTL expression is a feature of sporadic and familial Alzheimer's disease (AD), with human APPV717I neurons having less dynamic microtubules. We find that spines visited by dynamic microtubules are more resistant to Abeta1-42 and that TTL, by promoting microtubule entry into spines, prevents Abeta1-42-induced spine pruning. Our results demonstrate that the Tyr/deTyr cycle regulates synaptic plasticity, is protective against spine injury, and that tubulin re-tyrosination is lost in AD, providing evidence that a defective Tyr/deTyr cycle may contribute to neurodegeneration.

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“…After injury, peripheral axons form a growth cone invaded by dynamic MTs while axon shafts contain more stable MT bundles (Erturk, Hellal, Enes, & Bradke, 2007). In addition to tubulin nucleotide binding state, tubulin isoforms and the action of MT-associated proteins (MAPs), tubulin post-translational modifications (PTMs) are important regulators of MT dynamics (Moutin, Bosc, Peris, & Andrieux, 2020). Among several tubulin PTMs, α-tubulin acetylation, a tubulin PTM associated with stable MTs, plays an essential role in mechanosensory neurons (Yan et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Transthyretin promotes axon growth via regulation of microtubule dynamics and tubulin acetylation

Eira

Magalhães

Macedo

et al. 2021

Preprint

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Transthyretin (TTR), a plasma and cerebrospinal fluid protein, increases axon growth and organelle transport in sensory neurons. These TTR functions were suggested to underlie its activity in promoting nerve regeneration. While neurons extend their axons, the microtubule (MT) cytoskeleton is crucial for the segregation of functional compartments and axonal outgrowth. Herein, we investigated the hypothesis that TTR promotes axon elongation and regeneration by modulating MT dynamics. Indeed, we found that TTR KO mice have an intrinsic increase in dynamic MTs and reduced levels of acetylated α-tubulin in uninjured peripheral axons, and fail to modulate microtubule dynamics in response to sciatic nerve injury. Importantly, restoring acetylated α-tubulin levels of TTR KO DRG neurons using an HDAC6 inhibitor was sufficient to completely revert defective MT dynamics and neurite outgrowth. In summary, our results revealed a new role for TTR in the modulation of MT dynamics by regulating α-tubulin acetylation and support that this activity underlies TTR neuritogenic function.

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Tubulin post‐translational modifications control neuronal development and functions

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 71 publications

References 197 publications

Beyond Neuronal Microtubule Stabilization: MAP6 and CRMPS, Two Converging Stories

Beyond Neuronal Microtubule Stabilization: MAP6 and CRMPS, Two Converging Stories

Impaired α-tubulin re-tyrosination leads to synaptic dysfunction and is a feature of Alzheimer’s disease

Transthyretin promotes axon growth via regulation of microtubule dynamics and tubulin acetylation

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