Motor-dependent microtubule disassembly driven by tubulin tyrosination

Peris, Leticia; Wagenbach, Michael; Lafanechère, Laurence; Brocard, Jacques; Moore, Ayana T.; Kozielski, Frank; Job, Didier; Wordeman, Linda; Andrieux, Annie

doi:10.1083/jcb.200902142

Cited by 310 publications

(279 citation statements)

References 31 publications

(48 reference statements)

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“…We refer to this population of stable detyrosinated MTs as Glu MTs, to distinguish them from tyrosinated MTs (Tyr MTs) that are dynamic . MT detyrosination has been shown to abolish the plus-end tracking of CAP glycine proteins (Peris et al, 2006), inhibit MT depolymerization by kinesin-13 family motors (Peris et al, 2009) and increase the affinity of conventional kinesin to MTs (Dunn et al, 2008;Konishi and Setou, 2009;Kreitzer et al, 1999;Liao et al, 1999). In fibroblasts, the LPA and integrin pathway activates RhoA, which in turn acts through the formin mDia1 and several MT-and actin-binding proteins to capture and directly stabilize MTs at cortical sites (Andrés-Delgado et al, 2012;Bartolini and Gundersen, 2010;Bartolini et al, 2008;Bartolini et al, 2012;Cook et al, 1998;Eng et al, 2006;Goulimari et al, 2005;Goulimari et al, 2008;Gundersen et al, 1994;Nagasaki and Gundersen, 1996;Palazzo et al, 2001a;Palazzo et al, 2004;Wen et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Amyloid beta1-42 peptide regulates microtubule stability independently of tau

Pianu

Lefort

Thuiliere

et al. 2014

Journal of Cell Science

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Interference with microtubule stability by beta-amyloid peptide (Ab) has been shown to disrupt dendritic function and axonal trafficking, both early events in Alzheimer's disease. However, it is unclear whether Ab regulation of microtubule dynamics can occur independently of its action on tau. RhoA has been implicated in neurotoxicity by Ab but the mechanism by which this activation generates cytoskeletal changes is also unclear. We found that oligomeric Ab 1-42 induced the formation of stable detyrosinated microtubules in NIH3T3 cells and this function resulted from the activation of a RhoA-dependent microtubule stabilization pathway regulated by integrin signaling and the formin mDia1. Induction of microtubule stability by Ab was also initiated by dimerization of APP and required caspase activity, two previously characterized regulators of neurotoxicity downstream of Ab. Finally, we found that this function was conserved in primary neurons and abolished by Rho inactivation, reinforcing a link between induction of stable detyrosinated microtubules and neuropathogenesis by Ab. Our study reveals a novel activity of Ab on the microtubule cytoskeleton that is independent of tau and associated with pathways linked to microtubule stabilization and Ab-mediated neurotoxicity.

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Section: Introductionmentioning

confidence: 99%

Amyloid beta1-42 peptide regulates microtubule stability independently of tau

Pianu

Lefort

Thuiliere

et al. 2014

Journal of Cell Science

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“…L'accumulation de telles modifications a longtemps été considérée comme une consé-quence de la stabilisation d'un sous-ensemble de MT. Cette vue a changé radicalement avec la démonstra-tion que la détyrosination stabilise indirectement les MT en inhibant le recrutement de moteurs moléculaires dépolymérisants [10].…”

Section: Modifications Post-traductionnelles De La Tubuline Et Envirounclassified

Compartimentation et plasticité du réseau microtubulaire

Pilon

Poüs

2013

Med Sci (Paris)

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> La structuration du cytoplasme repose en grande partie sur le cytosquelette au sein duquel le réseau de microtubules joue de multiples rôles, notamment dans le trafic intracellulaire et la signalisation. Certaines fonctions cellulaires nécessitent des microtubules hautement dynamiques, alors que d'autres utilisent des microtubules stables où la tubuline peut être fortement modifiée. Des données récentes sur les mécanismes de contrôle de la dynamique des microtubules et de leurs modifications posttraductionnelles, notamment de l'acétylation de la tubuline, révèlent la grande plasticité des microtubules et mettent en lumière l'importance de leur compartimentation structurale et fonctionnelle. < aussi l'appareil de Golgi, l'enveloppe nucléaire ou des régions sous-corticales selon les types cellulaires), alors que le bout « plus » est orienté vers la périphérie cellulaire. L'échange de sous-unités de tubuline au bout « plus » s'effectue dans deux conformations différentes. En phase de croissance, la tubuline incorporée forme un feuillet dont les côtés se rapprochent pour fermer le MT à la manière d'une fermeture éclair. En phase de désassemblage, le MT présente une courbure des protofilaments vers l'extérieur de la paroi microtubulaire. Chaque tubuline possède un site de liaison des nucléotides guanidiques. Le site d'-tubuline, qui est orienté vers l'interface , reste bloqué sous une forme liant le GTP. À l'inverse, le site de la -tubuline -dit échangeable -peut lier le GTP ou le GDP. Le passage de l'état GDP à GTP s'effectue par échange nucléotidique et permet l'incorporation de la tubuline dans un MT. Le contact entre la sous-unité  d'un dimère récemment incorporé et la sous-unité  d'un dimère incorporé antérieurement stimule l'activité GTPase de la tubuline (qui se comporte ainsi comme une GTPase-activating protein intrinsèque). Dans un MT en croissance, les dernières sous-unités incorporées lient encore le GTP (c'est la notion de coiffe de tubuline-GTP), tandis que le reste du polymère reste associé au GDP. La structure de la forme GTP étant plus droite que celle de la forme GDP (qui présente une légère angulation entre ses sous-unités  et ), une coiffe de tubuline-GTP à l'extrémité « plus » exerce une contrainte conformationnelle qui stabilise le MT en empêchant les protofilaments d'adopter leur courbure naturelle. Si la coiffe est perdue, la contrainte est levée, les protofilaments se courbent et le MT se dépolymérise, libérant la tubuline-GDP (Figure 1).

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“…Tyrosination and detyrosination of microtubules is dependent on the equilibrium of tyrosine-tubulin ligase (TTL) and carboxypeptidase activities (CpA), which add and remove tyrosine from the C-terminal EEY motif of α-tubulin. Detyrosination controls the rescue/catastrophe ratio by regulating MCAK, a kinesin depolymerizing factor whose interaction is regulated by EEY motifs [88]. Detyrosination of microtubules has been observed during T cell activation, and is promoted by a forminlike protein (IFN2).…”

Section: Box1mentioning

confidence: 99%

Immune synapse: conductor of orchestrated organelle movement

Martín-Cófreces¹,

Baixauli²,

Sánchez-Madrid³

2014

Trends in Cell Biology

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SummaryTo ensure proper cell function, intracellular organelles are not randomly distributed within the cell, but polarized and highly constrained by the cytoskeleton and associated adaptor proteins. This relationship between distribution and function was originally found in neurons and epithelial cells; however, recent evidence suggests that it is a more general phenomenon that occurs in many highly specialized cells including the immune T cells. Recent studies reveal that the orchestrated redistribution of organelles is dependent on antigen specific activation and immune-synapse formation of T cells. This review highlights the functional implications of organelle polarization in early T cell activation and examines recent findings on how the immune synapse sets the rhythm of organelle motion and the spread of the activation signal to the nucleus. KeywordsImmune synapse; microcluster; signalosome; mitochondria; vesicle; microtubule Overview of the immune synapseT cell activation starts with an initial wave of signalling that depends on the activation of surface receptors, but subsequent propagation of the signal appears to depend on intracellular compartments, in a sequence driven by the actin and tubulin cytoskeletons [1]. The study of neural synapses highlighted the importance of cell polarity and the specific localization of organelles and clusters of receptors at the pre-and post-synaptic terminals. Despite its transient nature, recent evidence shows that the immune synapse (IS) shares these same neuronal features.The IS is the interface between a T lymphocyte and an antigen presenting cell (APC). During the formation and stabilization of the IS, membrane microdomains and the cytoskeleton reorganize and promote the segregation of membrane and intracellular signaling proteins within the T cell, such as the T cell receptor (TCR), integrins, tyrosine Europe PMC Funders Author ManuscriptsEurope PMC Funders Author Manuscripts kinases and scaffold proteins such as Linker for activation of T cells (LAT) (Figure 1 and Glossary). The TCR and associated molecules (TCR signalosomes) form microclusters that move to congregate in the central area (central supramolecular activation cluster; cSMAC) of the IS, whereas adhesion receptors such as integrins reorganize in a surrounding external ring called the peripheral or pSMAC ( Figure 2) [2]. In addition, phosphorylation and dephosphorylation, protein-protein interactions and degradation of important molecules such as the TCR-accompanying CD3 complex, tyrosine kinases, phosphatases and adaptor molecules also control receptor activation [3,4]. The polarization of several organelles occurs during T cell stimulation with important roles, such as the centrosome, Golgi apparatus, mitochondria, endoplasmic reticulum and the multivesicular bodies (MVB) [5][6][7][8][9][10]. These rearrangements at the IS promote the activation of signaling pathways that propagate to the nucleus. Signals activating nuclear transcription factors in combination with polarity proteins, such as partit...

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Motor-dependent microtubule disassembly driven by tubulin tyrosination

Cited by 310 publications

References 31 publications

Amyloid beta1-42 peptide regulates microtubule stability independently of tau

Amyloid beta1-42 peptide regulates microtubule stability independently of tau

Compartimentation et plasticité du réseau microtubulaire

Immune synapse: conductor of orchestrated organelle movement

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