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Grenoble Institut des Neurosciences

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Team "Neurocytoskeleton Dynamics and Structure"

Directors: Isabelle ARNAL and Annie ANDRIEUX

Our team aims to elucidate the contribution of the cytoskeleton in neuronal functions, both in normal and pathological contexts. We investigate cytoskeleton dynamics and structural properties in model systems of various complexities (biomimetic assays, cellular and animal models) and using multidisciplinary approaches (structural biology, cell biology, advanced light and cryo-electron microscopy).

The objective of the team “Neuro-cytoskeleton Dynamics and Structure” is to elucidate the mechanisms underlying cytoskeleton organisation in neuronal development and plasticity, and to understand how these mechanisms are deregulated in pathological conditions. More specifically, we aim at deciphering how MAPs -elaborate and control various MT arrangements -regulate actin behaviour and -contribute to the MT-actin crosstalk.

Research themes and techniques used

Microtubules, major cytoskeletal elements, are central to neuronal architecture and activity. Microtubules can be dynamic or stable and exist as single polymers or bundled networks. Microtubules cooperate with actin, another cytoskeletal component in neuron, this synergy being crucial for neuronal development and functions. By regulating microtubule stability and self-organisation, Microtubule-Associated Proteins (MAPs) are key microtubule regulators. Recent evidences including our work show that MAPs can also directly bind actin. Cytoskeleton alterations, including those resulting from MAPs dysfunctions, are linked to brain development disorders and neurodegenerative diseases.

Techniques used

Molecular biology and biochemistry: cloning, protein expression and purification, protein interactions
Biomimetic assays: in vitro reconstitution of microtubule and actin behaviour
Cell biology: primary cultures of neurons, subcellular localisation of proteins, cytoskeleton dynamics
Microscopy: confocal and spinning disc microscopy, confocal airyscan microscopy, live imaging, Total-Internal Reflexion Fluorescence (TIRF) microscopy, single molecule TIRF imaging, expansion microscopy, electron cryo-microscopy and -tomography, 3D reconstructions (etomo, relion)

Publications

Cuveillier C, Delaroche J, Seggio M, Gory-Fauré S, Bosc C, Denarier E, Bacia M, Schoehn G, Mohrbach H, Kuli? I, Andrieux, Arnal I, Delphin C (2020). MAP6 is an intraluminal protein that induces neuronal microtubules to coil. Science Adv 6:eaaz4344.

Serre L, Stoppin-Mellet V, Arnal I (2019) Adenomatous Polyposis Coli as a Scaffold for Microtubule End-Binding Proteins. J Mol Biol 431, 1993-2005.

Denarier E, Brousse C, Sissoko A, Andrieux A, Boscheron C (2019) A neurodevelopmental TUBB2B beta-tubulin mutation impairs Bim1 (yeast EB1)-dependent spindle positioning. Biol Open 29:8.

Prezel E, Elie A, Delaroche J, Stoppin-Mellet V, Bosc C, Serre L, Fourest-Lieuvin A, Andrieux A, Vantard M, Arnal I (2018) Tau can switch microtubule network organizations: from random networks to dynamic and stable bundles. Mol Biol Cell 29:154-165.

Peris L, Bisbal M, Martinez-Hernandez J, Saoudi Y, Jonckheere J, Rolland M, Sebastien M, Brocard J, Denarier E, Bosc C, Guerin C, Gory-Fauré S, Deloulme JC, Lanté F, Arnal I, Buisson A, Goldberg Y, Blanchoin L, Delphin C, Andrieux A (2018) A key function for microtubule-associated-protein 6 in activity-dependent stabilisation of actin filaments in dendritic spines. Nat Comm 9:3775.

Jonckheere J, Deloulme JC, Dall'Igna G, Chauliac N, Pelluet A, Nguon AS, Lentini C, Brocard J, Denarier E, Brugière S, Couté Y, Heinrich C, Porcher C, Holtzmann J, ANDRIEUX A, Suaud-Chagny MF, Gory-Faure S (2018) Short- and long-term efficacy of electroconvulsive stimulation in animal models of depression: The essential role of neuronal survival. Brain Stimul 11:1336-1347.

Aillaud C, Bosc C, Peris L, Bosson A, Heemeryck P, Van Dijk J, Le Friec J, Boulan B, Vossier F, Sanman LE, Syed S, Amara N, Couté Y, Lafanechère L, Denarier E, Delphin C, Pelletier L, Humbert S, Bogyo M, Andrieux A, Rogowski K, Moutin MJ (2017) Vasohibins/SVBP are tubulin carboxypeptidases (TCPs) that regulate neuron differentiation. Science 358:1448-1453.

Ramirez-Rios S, Denarier E, Prezel E, Vinit A, Stoppin-Mellet V, Devred F, Barbier P, Peyrot V, Sayas CL, Avila J, Peris L, Andrieux A, Serre L, Fourest-Lieuvin A, Arnal I (2016) Tau antagonizes end-binding protein tracking at microtubule ends through a phosphorylation-dependent mechanism. Mol Biol Cell 27:2924-2934.

Elie A, Prezel E, Guérin C, Denarier E, Ramirez-Rios S, Serre L, Andrieux A, Fourest-Lieuvin A, Blanchoin L, Arnal I (2015) Tau co-organizes dynamic microtubule and actin networks. Sci Rep 5:9964.

Deloulme JC, Gory-Faure S, Mauconduit F, Chauvet S, Jonckheere J, Boulan B, Mire E, Xue J, Jany M, Maucler C, Deparis AA, Montigon O, Daoust A, Barbier EL, Bosc C, Deglon N, Brocard J, Denarier E, Le Brun I, Pernet-Gallay K, Vilgrain I, Robinson PJ, Lahrech H, Mann F, Andrieux A (2015) Microtubule-associated protein 6 mediates neuronal connectivity through Semaphorin 3E-dependent signalling for axonal growth. Nat Commun 6:7246.

Publications of the team

Updated on April 6, 2021

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