Extracellular matrix proteins and adhesion proteins involved in synapse formation, its plasticity and the establishment of neuronal conectivity. They also coordinate the pre- and postsynaptic activities and the maturation of the synapse in the nervous system. To date, however their are few datas that highlight molecular mecanisms to which that matricials molecules control the synaptic development. How Extracellular matrix proteins control the main steps of the synapse’s formation like the axonal guidance, the formation and maturation of the synaptic contact ? In order to answer this questions, the biological system used by our team is the neuromuscular junction in vertebrates. This synapse is an excellent modèle for the study of synaptogenesis and has allowed notable steps forward in this domain.

The main goal of our team is :

1. Identify proteins involved in axonal guidance toward their targeted muscules
2. Reveal interactions of a specific collagen, CoIQ with others Extracellular Matrix proteins and to dissect the sigalisation cascade induced byCoIQ in the postsynaptic element’s formation.
3. Understand microtubules and associated proteins (MAP) role in the transduction of a signal coming from the extracellular matrix.

To answer to these questions, we combine In vivo studies in knock-out mice and in vitro in culture systems. These 3 themes are associated to synapse’s pathologies which are studied in parallel on animal models  for these pathologies

Themes of research :

• Identification of molecules of axonal guidance involved in the formation of the neuromuscular junction.
  Laure Strochlic
• Identification of the CoIQ’s partners in the extracellular matrix and dissection of the signaling cascade induced by the protein CoIQ in the maturation of the postsynaptic element.
  Alexandre Dobbertin

Collaborations :

• University of Ottawa, Canada
• UMR 5161 CNRS-ENSLyon-INRA, France
• UMR 5534 CNRS-Université Lyon 1, France

Recent Publications

Articles

• Loss of C9ORF72 impairs autophagy and synergizes with polyQ Ataxin-2 to induce motor neuron dysfunction and cell death.
  Sellier C, Campanari ML, Julie Corbier C, Gaucherot A, Kolb-Cheynel I, Oulad-Abdelghani M, Ruffenach F, Page A, Ciura S, Kabashi E, Charlet-Berguerand N : EMBO J, 2016
• Loss of VPS13C Function in Autosomal-Recessive Parkinsonism Causes Mitochondrial Dysfunction and Increases PINK1/Parkin-Dependent Mitophagy.
  Lesage S, Drouet V, Majounie E, Deramecourt V, Jacoupy M, Nicolas A, Cormier-Dequaire F, Hassoun SM, Pujol C, Ciura S, Erpapazoglou Z, Usenko T, Maurage CA, Sahbatou M, Liebau S, Ding J, Bilgic B, Emre M, Erginel-Unaltuna N, Guven G, Tison F, Tranchant C, Vidailhet M, Corvol JC, Krack P, Leutenegger AL, Nalls MA, Hernandez DG, Heutink P, Gibbs JR, Hardy J, Wood NW, Gasser T, Durr A, Deleuze JF, Tazir M, Destée A, Lohmann E, Kabashi E, Singleton A, Corti O, Brice A : Am J Hum Genet, 2016
• The most prevalent genetic cause of ALS-FTD, C9orf72 synergizes the toxicity of ATXN2 intermediate polyglutamine repeats through the autophagy pathway.
  Ciura S, Sellier C, Campanari ML, Charlet-Berguerand N, Kabashi E : Autophagy, 2016
• Implication of NPM1 phosphorylation and preclinical evaluation of the nucleoprotein antagonist N6L in prostate cancer.
  Destouches D, Sader M, Terry S, Marchand C, Maillé P, Soyeux P, Carpentier G, Semprez F, Céraline J, Allory Y, Courty J, De La Taille A, Vacherot F : Oncotarget, 2016
• ΔN-TRPV1: A Molecular Co-detector of Body Temperature and Osmotic Stress.
  Zaelzer C, Hua P, Prager-Khoutorsky M, Ciura S, Voisin DL, Liedtke W, Bourque CW : Cell Rep, 2015
• Two novel COLVI long chains in zebrafish that are essential for muscle development.
  Ramanoudjame L, Rocancourt C, Lainé J, Klein A, Joassard L, Gartioux C, Fleury M, Lyphout L, Kabashi E, Ciura S, Cousin X, Allamand V : Hum Mol Genet, 2015
• Defining the genetic connection linking amyotrophic lateral sclerosis (ALS) with frontotemporal dementia (FTD).
  Lattante S, Ciura S, Rouleau GA, Kabashi E : Trends Genet, 2015
• Implication de la molécule X dans la récidive du cancer de prostate (CaP) localisé.
  Champy C, Semprez F, El Sayed I, Maille P, Soyeux P, Allory Y, Vacherot F, De La Taille A, Firlej V : Prog Urol, 2015
• CRIPTO overexpression promotes mesenchymal differentiation in prostate carcinoma cells through parallel regulation of AKT and FGFR activities.
  Terry S, El-Sayed IY, Destouches D, Maillé P, Nicolaiew N, Ploussard G, Semprez F, Pimpie C, Beltran H, Londono-Vallejo A, Allory Y, de la Taille A, Salomon DS, Vacherot F : Oncotarget, 2015
• Clinical value of ERG, TFF3, and SPINK1 for molecular subtyping of prostate cancer.
  Terry S, Nicolaiew N, Basset V, Semprez F, Soyeux P, Maillé P, Vacherot F, Ploussard G, Londoño-Vallejo A, de la Taille A, Allory Y : Cancer, 2015
• A critical and previously unsuspected role for doublecortin at the neuromuscular junction in mouse and human.
  Bourgeois F, Messéant J, Kordeli E, Petit JM, Delers P, Bahi-Buisson N, Bernard V, Sigoillot SM, Gitiaux C, Stouffer M, Francis F, Legay C : Neuromuscul Disord, 2015
• HuR Mediates Changes in the Stability of AChR β-Subunit mRNAs after Skeletal Muscle Denervation.
  Joassard OR, Bélanger G, Karmouch J, Lunde JA, Shukla AH, Chopard A, Legay C, Jasmin BJ : J Neurosci, 2015
• MuSK frizzled-like domain is critical for mammalian neuromuscular junction formation and maintenance.
  Messéant J, Dobbertin A, Girard E, Delers P, Manuel M, Mangione F, Schmitt A, Le Denmat D, Molgó J, Zytnicki D, Schaeffer L, Legay C, Strochlic L : J Neurosci, 2015
• Sqstm1 knock-down causes a locomotor phenotype ameliorated by rapamycin in a zebrafish model of ALS/FTLD.
  Lattante S, de Calbiac H, Le Ber I, Brice A, Ciura S, Kabashi E : Hum Mol Genet, 2014
• AlphaII-spectrin participates in the surface expression of cell adhesion molecule L1 and neurite outgrowth
  Trinh-Trang-Tan MM, Bigot S, Picot J, Lecomte MC, Kordeli E : Exp Cell Res, 2014
• TREM2 mutations are rare in a French cohort of patients with frontotemporal dementia.
  Lattante S, Le Ber I, Camuzat A, Dayan S, Godard C, Van Bortel I, De Septenville A, Ciura S, Brice A, Kabashi E : Neurobiol Aging, 2013
• Loss of function of C9orf72 causes motor deficits in a zebrafish model of amyotrophic lateral sclerosis.
  Ciura S, Lattante S, Le Ber I, Latouche M, Tostivint H, Brice A, Kabashi E : Ann Neurol, 2013
• Developmental consequences of the ColQ/MuSK interactions
  Karmouch J, Dobbertin A, Sigoillot S, Legay C : Chem Biol Interact, 2013
• Methylene blue protects against TDP-43 and FUS neuronal toxicity in C. elegans and D. rerio.
  Vaccaro A, Patten SA, Ciura S, Maios C, Therrien M, Drapeau P, Kabashi E, Parker JA : PLoS One, 2012
• Wnt4 participates in the formation of vertebrate neuromuscular junction.
  Strochlic L, Falk J, Goillot E, Sigoillot S, Bourgeois F, Delers P, Rouvière J, Swain A, Castellani V, Schaeffer L, Legay C : PLoS One, 2012
• Existence of tenascin-C isoforms in rat that contain the alternatively spliced AD1 domain are developmentally regulated during hippocampal development
  Garwood J, Theocharidis U, Calco V, Dobbertin A, Faissner A : Cell Mol Neurobiol, 2012
• Wnt4 participates in the formation of vertebrate neuromuscular junction
  Strochlic L, Falk J, Goillot E, Sigoillot S, Bourgeois F, Delers P, Rouvière J, Swain A, Castellani V, Schaeffer L, Legay C : PLoS One, 2012