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

• Con­gen­i­tal myas­thenic syn­dromes with acetyl­cholinesterase defi­cien­cy, the patho­phys­i­o­log­i­cal mech­a­nisms.
  Legay C : Ann N Y Acad Sci, 2018
• Wnt pro­teins con­tribute to neu­ro­mus­cu­lar junc­tion for­ma­tion through dis­tinct sig­nal­ing path­ways.
  Messéant J, Ezan J, Del­ers P, Gle­bov K, Mar­chi­ol C, Lager F, Renault G, Tis­sir F, Mont­couquiol M, Sans N, Legay C, Strochlic L : Devel­op­ment, 2017
• Mov­ing for­ward with the neu­ro­mus­cu­lar junc­tion.
  Legay C, Mei L : J Neu­rochem, 2017
• Neu­ro­mus­cu­lar Junc­tion Impair­ment in Amy­otroph­ic Lat­er­al Scle­ro­sis: Reassess­ing the Role of Acetyl­cholinesterase.
  Cam­pa­nari ML, Gar­cía-Ayl­lón MS, Ciu­ra S, Sáez-Valero J, Kabashi E : Front Mol Neu­rosci, 2016
• Neu­ro­mus­cu­lar junc­tion imma­tu­ri­ty and mus­cle atro­phy are hall­marks of the ColQ-defi­cient mouse, a mod­el of con­gen­i­tal myas­thenic syn­drome with acetyl­cholinesterase defi­cien­cy.
  Sigoil­lot SM, Bour­geois F, Kar­mouch J, Mol­gó J, Dob­bertin A, Cheva­lier C, Houl­gat­te R, Léger J, Legay C : FASEB J, 2016
• 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
• 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