title: Microtubule-associated protein 6 mediates neuronal connectivity through Semaphorin 3E-dependent signalling for axonal growth.
abstract: Structural microtubule associated proteins (MAPs) stabilize microtubules, a property that was thought to be essential for development, maintenance and function of neuronal circuits. However, deletion of the structural MAPs in mice does not lead to major neurodevelopment defects. Here we demonstrate a role for MAP6 in brain wiring that is independent of microtubule binding. We find that MAP6 deletion disrupts brain connectivity and is associated with a lack of post-commissural fornix fibres. MAP6 contributes to fornix development by regulating axonal elongation induced by Semaphorin 3E. We show that MAP6 acts downstream of receptor activation through a mechanism that requires a proline-rich domain distinct from its microtubule-stabilizing domains. We also show that MAP6 directly binds to SH3 domain proteins known to be involved in neurite extension and semaphorin function. We conclude that MAP6 is critical to interface guidance molecules with intracellular signalling effectors during the development of cerebral axon tracts.
authors.affiliation: 1] INSERM, U836, F-38000 Grenoble, France [2] Univ. Grenoble Alpes, Grenoble Institut Neurosciences, F-38000 Grenoble, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Deloulme
authors.affiliation: 1] INSERM, U836, F-38000 Grenoble, France [2] Univ. Grenoble Alpes, Grenoble Institut Neurosciences, F-38000 Grenoble, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Gory-Fauré
authors.affiliation: 1] INSERM, U836, F-38000 Grenoble, France [2] Univ. Grenoble Alpes, Grenoble Institut Neurosciences, F-38000 Grenoble, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Mauconduit
authors.affiliation: Aix-Marseille Université, CNRS, IBDM UMR 7288, 13288 Marseille, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Chauvet
authors.affiliation: 1] INSERM, U836, F-38000 Grenoble, France [2] Univ. Grenoble Alpes, Grenoble Institut Neurosciences, F-38000 Grenoble, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Jonckheere
authors.affiliation: 1] INSERM, U836, F-38000 Grenoble, France [2] Univ. Grenoble Alpes, Grenoble Institut Neurosciences, F-38000 Grenoble, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Boulan
authors.affiliation: Aix-Marseille Université, CNRS, IBDM UMR 7288, 13288 Marseille, France.
authors.forename: Erik
authors.initials: E
authors.lastname: Mire
authors.affiliation: Cell Signalling Unit, Children's Medical Research Institute, University of Sydney, Wentworthville, New South Wales 2145, Australia.
authors.forename: Jing
authors.initials: J
authors.lastname: Xue
authors.affiliation: 1] INSERM, U836, F-38000 Grenoble, France [2] Univ. Grenoble Alpes, Grenoble Institut Neurosciences, F-38000 Grenoble, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Jany
authors.affiliation: 1] INSERM, U836, F-38000 Grenoble, France [2] Univ. Grenoble Alpes, Grenoble Institut Neurosciences, F-38000 Grenoble, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Maucler
authors.affiliation: 1] INSERM, U836, F-38000 Grenoble, France [2] Univ. Grenoble Alpes, Grenoble Institut Neurosciences, F-38000 Grenoble, France.
authors.forename: Agathe A
authors.initials: AA
authors.lastname: Deparis
authors.affiliation: 1] INSERM, U836, F-38000 Grenoble, France [2] Univ. Grenoble Alpes, Grenoble Institut Neurosciences, F-38000 Grenoble, France [3] Centre Hospitalier Universitaire de Grenoble, IRMaGe, 38043 Grenoble, France [4] CNRS, UMS 3552, 38042 Grenoble, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Montigon
authors.affiliation: 1] INSERM, U836, F-38000 Grenoble, France [2] Univ. Grenoble Alpes, Grenoble Institut Neurosciences, F-38000 Grenoble, France.
authors.forename: Alexia
authors.initials: A
authors.lastname: Daoust
authors.affiliation: 1] INSERM, U836, F-38000 Grenoble, France [2] Univ. Grenoble Alpes, Grenoble Institut Neurosciences, F-38000 Grenoble, France.
authors.forename: Emmanuel L
authors.identifier: 0000000249521240
authors.initials: EL
authors.lastname: Barbier
authors.affiliation: 1] INSERM, U836, F-38000 Grenoble, France [2] Univ. Grenoble Alpes, Grenoble Institut Neurosciences, F-38000 Grenoble, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Bosc
authors.affiliation: 1] Lausanne University Hospital (CHUV), Department of Clinical Neurosciences (DNC), Laboratory of Cellular and Molecular Neurotherapies (LCMN), 1011 Lausanne, Switzerland [2] Lausanne University Hospital (CHUV), Neuroscience Research Center (CRN), 1011 Lausanne, Switzerland.
authors.forename: Nicole
authors.identifier: 0000000344759476
authors.initials: N
authors.lastname: Deglon
authors.affiliation: 1] INSERM, U836, F-38000 Grenoble, France [2] Univ. Grenoble Alpes, Grenoble Institut Neurosciences, F-38000 Grenoble, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Brocard
authors.affiliation: 1] INSERM, U836, F-38000 Grenoble, France [2] Univ. Grenoble Alpes, Grenoble Institut Neurosciences, F-38000 Grenoble, France [3] CEA, iRTSV, F-38000 Grenoble, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Denarier
authors.affiliation: 1] Univ. Grenoble Alpes, Grenoble Institut Neurosciences, F-38000 Grenoble, France [2] INSERM, U1036, 38054 Grenoble, France [3] CEA, iRTSV, F-38000 Grenoble, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Le Brun
authors.affiliation: 1] INSERM, U836, F-38000 Grenoble, France [2] Univ. Grenoble Alpes, Grenoble Institut Neurosciences, F-38000 Grenoble, France.
authors.forename: Karin
authors.initials: K
authors.lastname: Pernet-Gallay
authors.affiliation: 1] Univ. Grenoble Alpes, Grenoble Institut Neurosciences, F-38000 Grenoble, France [2] INSERM, U1036, 38054 Grenoble, France [3] INSERM, U1036, 38054 Grenoble, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Vilgrain
authors.affiliation: Cell Signalling Unit, Children's Medical Research Institute, University of Sydney, Wentworthville, New South Wales 2145, Australia.
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Robinson
authors.affiliation: 1] INSERM, U836, F-38000 Grenoble, France [2] Univ. Grenoble Alpes, Grenoble Institut Neurosciences, F-38000 Grenoble, France [3] CEA, LETI, CLINATEC, MINATEC Campus, F-38054 Grenoble, France.
authors.forename: Hana
authors.initials: H
authors.lastname: Lahrech
authors.affiliation: Aix-Marseille Université, CNRS, IBDM UMR 7288, 13288 Marseille, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Mann
authors.affiliation: 1] INSERM, U836, F-38000 Grenoble, France [2] Univ. Grenoble Alpes, Grenoble Institut Neurosciences, F-38000 Grenoble, France [3] CEA, iRTSV, F-38000 Grenoble, France.
authors.forename: Annie
authors.initials: A
authors.lastname: Andrieux
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D003598:Cytoskeletal Proteins; D056324:Diffusion Tensor Imaging; D020712:Fornix, Brain / Q000196:embryology* / Q000378:metabolism / Q000473:pathology; D006023:Glycoproteins / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008279:Magnetic Resonance Imaging; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D009434:Neural Pathways / Q000196:embryology / Q000378:metabolism; D016501:Neurites / Q000378:metabolism; D056347:Neuroanatomical Tract-Tracing Techniques; D009474:Neurons / Q000378:metabolism*; D009929:Organ Size; D039961:Semaphorins; D018909:src Homology Domains
chemical_list: D003598:Cytoskeletal Proteins; D006023:Glycoproteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C491893:Mtap6 protein, mouse; C111150:Sema3e protein, mouse; D039961:Semaphorins