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Physiopathology of the Cytoskeleton

Team 1 Physiopathology of the Cytoskeleton focuses its research on microtubules, their effectors and functions within a physiological or pathological environment.                   


Research themes

Our team Physiopathology of the Cytoskeleton is a world leader in the study of microtubular effectors from cells in culture up to the living animal. Hence, our group have shown that families of effectors such as STOP proteins and tubulin-modifying enzymes are major actors in brain functions. Moreover, tubulin modifications are also crucial for tumor progression. Our present work focuses on the contribution of microtubules and their effectors in cellular functions: mitosis, neuronal differentiation, neuronal networks plasticity. Learn more…

  • Tubulin-modifying enzymes : Moutin MJo, Aillaud C, Bosc C, Saoudi A
  • In vitro and in vivo microtubular dynamics; study of the MT effectors : Valiron O, Delphin C, Seggio M, Soleilhac JM
  • Microtubular effectors in the yeast : Boscheron C, Denarier E
  • STOP/SL21 proteins and neuronal networks : Deloulme JC, Gory S, Jonckheere J, Holtzmann J
  • STOP proteins and neuronal differentiation : Peris L,, Bosc C, Brocard J, Lebrun I

Techniques

  • Molecular biology plasmid constructs, cloning and sub-cloning, PCR, expression of recombinant protein
  • Biochemistry purification of proteins and antibodies, search for interacting protein partners, yeast double-hybrid screening, immunoprecipitation
  • Cell biology neuronal cell lines and primary neuronal cell cultures, fluorescence and confocal imaging, videomicroscopy
  • Animal studies production of transgenic and conditional KO mouse lines, phenotypic characterization: anatomy, behavior, electronic microscopy

    Publications

    • 2013: Lefèvre J., Savarin P., Gans P., Hamon L., Clément M.-J., David M.-O., Bosc C., Andrieux A. and Curmi P.A. Structural basis for the association of MAP6 protein with microtubules and its regulation by calmodulin. J. Biol. Chem. 288: 24910.
    • 2013: Poirier K., Lebrun N., Broix L., Tian G., Saillour Y., Boscheron C., Parrini E., Valence S., [20 co-authors], Zelenika D., Andrieux A., Francis F., Guerrini R., Cowan N.J., Bahi-Buisson N. and Chelly J. Mutations in TUBG1, DYNC1H1, KIF5C and KIF2A cause malformations of cortical development and microcephaly. Nat. Genet. 45: 639.
    • 2013: Volle J., Brocard J., Saoud M., Gory-Faure S., Brunelin J, Andrieux A. and Suaud-Chagny M.-F.. Reduced expression of STOP/MAP6 in mice leads to cognitive deficits. Schizophr. Bull. 39: 969.
    • 2013: Poirier K., Lebrun N., Broix L., Tian G., Saillour Y., Boscheron C., ..., Andrieux A., Francis F., Guerrini R., Cowan N.-J., Bahi-Buisson N. and Chelly J. Mutations in TUBG1, DYNC1H1, KIF5C and KIF2A cause malformations of cortical development and microcephaly. Nat. Genet. xx: xxx.
    • 2013: Nissou M.-F., Brocard J., El Atifi M., Guttin A., Andrieux A., Berger F., Issartel J.-P. and Wion D. The transcriptomic response of mixed neuron-glial cell cultures to 1,25-dihydroxyvitamin d3 includes genes limiting the progression of neurodegenerative diseases. J Alzheimer's Dis. 35: 553.
    • 2013: Alfaidy N., Chauvet S., Donadio-Andrei S., Salomon A., Saoudi Y., Richaud P., Aude-Garcia C., Hoffmann P., Andrieux A., Moulis J.-M., Feige J.J. and Benharouga M. Prion protein expression and functional importance in developmental angiogenesis: role in oxidative stress and copper homeostasis. Antioxid. Redox Signal 18: 400.
    • 2012: Fournet V., de Lavilléon G., Schweitzer A., Giros B., Andrieux A. and Martres MP. Both chronic treatments by epothilone D and fluoxetine increase the short-term memory and differentially alter the mood status of STOP/MAP6 KO mice. J. Neurochem. 123: 982.
    • 2012: 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. J. Biol. Chem. 287: 35127.
    • 2012: Tadmouri A., Kiyonaka S., Barbado M., Rousset M., Fablet K., Sawamura S., Bahembera E., Pernet-Gallay K., Arnoult C., Miki T., Sadoul K., Gory-Fauré S., Lambrecht C., Lesage F., Akiyama S., Kochbin S., Baulande S., Jansses V., Andrieux A., Dolmetsch R., Ronjat M., Mori Y. and De Waard M. Cacnb4 directly couples electrical activity to gene expression, a process defective in juvenile epilepsy. EMBO J. 31: 3730.
    • 2012 : Arama J., Boulay AC., Bosc C., Delphin C., Loew D., Rostaing P., Amigou E., Esan P., Wingertsmann L., Guillaud L., Andrieux A., Giaume C. and Cohen-Salmon M. Bmcc1s, a novel brain-isoform of Bmcc1, affects cell morphology by regulating MAP6/STOP functions. PLoS One 7: e35488.
    • 2012 : Roth S., Bisbal M., Brocard J., Bugnicourt G., Saoudi Y., Andrieux A. and Villard C. How morphological constraints affect axonal polarity in mouse neurons. PLoS One 7: e33623.
    • 2012 : Bosson A., Soleilhac JM., Valiron O., Job D., Andrieux A. and Moutin MJ. Cap-Gly proteins at microtubule plus ends: is EB1 detyrosination involved ? PLoS One 7: e33490.
    • 2012 : Roth S., Bugnicourt G., Bisbal M., Gory-Fauré S., Brocard J. and Villard C. Neuronal architectures with axo-dendritic polarity abon silicon nanowires. Small 8: 671-675.
    • 2012 : Fournet V., Schweitzer A., Chevarin C., Deloulme JC., Hamon M., Giros B., Andrieux A. and Martres MP. The deletion of STOP/MAP6 protein in mice triggers highly altered mood and impaired cognitive performances. J. Neurochem. 121: 99-114.
    • 2011 : Valiron O. New insights into microtubule elongation mechanisms. Commun. Integr. Biol. 4: 10-3.
    • 2011 : Moutin M.-J., Andrieux A. and Janke C. Microtubule polyglutamylation and neurodegeneration. Med. Sci. (Paris) 27: 464-467.

    Contracts

    • ANR Mental Health - Malaad; 25 k€/year, 2011-2014
    • INSERM, U836 team 1; 70 k€/year, recurrent
    • CEA, iRTSV/GPC; 5 k€/year, recurrent