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Cytoskeleton | Neurodegenerative diseases


UMR_S 1216 Inserm/University Grenoble Alpes/CEA/CHU Team 1

Group Physiopathology of the Cytoskeleton

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​Understand the intrinsic properties of microtubules, one of the constituents of the cytoskeleton, and their effectors; analyze their functions in the organization and operating of the central nervous system.

Published on 4 November 2016

Director

 





Annie Andrieux

Tel.: (33) 4 56 52 05 36
Fax: (33) 4 56 52 06 57


Address/Contact

Biosciences and Biotechnology Institute of Grenoble
CEA-Grenoble
17 avenue des Martyrs
38 054 Grenoble cedex09
France


Secretary
Tel.: (33) 4 56 52 05 36
Fax: (33) 4 56 52 06 57



Members of the group




Research themes

 

Legend: Axonal tracts including the fornix in WT and MAP6-KO brains, visualized using Diffusion Tensor Imaging (DTI).
The group "Physiopathology of the Cytoskeleton" investigates cytoskeletal microtubules, a major component of neuronal cells. Hundreds of effectors influence the microtubules' structure or function in various neuronal processes, e.g. proliferation of neuronal progenitors, neuronal differentiation, neuronal network maturation, synaptic plasticity, etc. Our team focuses more specifically on Microtubule-Associated Proteins of the MAP6 family on the one hand and enzymes that modify the C-terminal amino acid of tubulins (tyrosination/detyrosination cycle).

These microtubular effectors are studied at various levels in the group "Physiopathology of the Cytoskeleton", from structure to whole organisms, in order to understand the various levels of microtubules' regulation:

Tubulin: characterize the importance of specific C-terminal amino acids in the assembly of tubulin dimers, the formation of microtubules and their function in the yeast.

Tubulin-modifying enzymes: Describe the physiological impact of post-translational modifications of tubulin, such as C-terminal tyrosination / detyrosination of alpha-tubulin, on neuronal differentiation and neuronal plasticity in the adult.

Regulation of microtubules' dynamics in vitro: Analyze how MAP6 proteins and their partners influence the dynamic properties of microtubules and actin, in cell-free systems.

Neuronal differentiation and microtubule-associated protein 6 (MAP6): Understand the contribution of these proteins and their partners in neuronal development and synaptic connectivity.

Development of neuronal networks and defective neuronal connectivity: Study the anatomical and physiological consequences of the absence of specific MAPs in model mice.


Techniques used

Molecular biology: Plasmid constructions, cloning and sub-cloning, PCR, expression of recombinant proteins, lentivirus, CRISPR/Cas9
Biochemistry: Purification of proteins and antibodies, interaction of protein partners, yeast two-hybrid screening, immunoprecipitation, TIRF imaging, electronic microscopy
Cellular biology: Cell lines and primary cultures of neurons, classical or confocal fluorescence imaging, videomicroscopy, FRAP and STORM high resolution imaging
Animal models: Production of transgenic or conditional knockout mice, phenotypic assessment (anatomy, tractography using DTI and behavioral studies)


Key words

Cytoskeleton, microtubules, tubulin, tubulin-modifying enzymes, MAP6, neurodevelopment, neuropsychiatric diseases, cerebral plasticity


Key publications of the group

Deloulme JC, Gory-Fauré 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  and Andrieux A
Microtubule-associated protein 6 mediates neuronal connectivity through Semaphorin 3E-dependent signalling for axonal growth.
Nature Communications, 2015, 6: 7246

Tort O, Tanco S, Rocha C, Bieche I, Seixas C, Bosc C, Andrieux A, Moutin MJ, Xavier Aviles F, Lorenzo J and Janke C
The cytosolic carboxypeptidases CCP2 and CCP3 catalyze posttranslational removal of acidic amino acids.
Molecular Biology of the Cell, 2014, 25(19): 3017-3027

Daoust A, Saoudi Y, Brocard J, Collomb N, Batandier C, Bisbal M, Salome M, Andrieux A, Bohic S and Barbier EL
Impact of manganese on primary hippocampal neurons from rodents.
Hippocampus, 2014, 24(5): 598-610

Poirier K, Lebrun N, Broix L, Tian G, Saillour Y, Boscheron C, Parrini E, Valence S, Pierre BS, Oger M, Lacombe D, Genevieve D, Fontana E, Darra F, Cances C, Barth M, Bonneau D, Bernadina BD, N'Guyen S, Gitiaux C, Parent P, des Portes V, Pedespan JM, Legrez V, Castelnau-Ptakine L, Nitschke P, Hieu T, Masson C, Zelenika D, Andrieux A, Francis F, Guerrini R, Cowan NJ, Bahi-Buisson N and Chelly J
Mutations in TUBG1, DYNC1H1, KIF5C and KIF2A cause malformations of cortical development and microcephaly.
Nature Genetics, 2013, 45(6): 639-647

Volle J, Brocard J, Saoud M, Gory-Faure S, Brunelin J, Andrieux A and Suaud-Chagny MF
Reduced expression of STOP/MAP6 in mice leads to cognitive deficits.
Schizophr Bull, 2013, 39(5): 969-978

Delphin C, Bouvier D, Seggio M, Couriol E, Saoudi Y, Denarier E, Bosc C, Valiron O, Bisbal M, Arnal I and Andrieux A
MAP6-F is a temperature sensor that directly binds to and protects microtubules from cold-induced depolymerization.
Journal of Biological Chemistry, 2012, 287(42): 35127-35138

Rogowski K, van Dijk J, Magiera MM, Bosc C, Deloulme J-C, Bosson A, Peris L, Gold ND, Lacroix B, Grau MB, Bec N, Larroque C, Desagher S, Holzer M, Andrieux A, Moutin M-J and Janke C
A family of protein-deglutamylating enzymes associated with neurodegeneration.
Cell, 2010, 143(4): 564-578