Microtubule-associated protein 6 mediates neuronal connectivity through Semaphorin 3E-dependent signalling for axonal growth

Jean-Christophe Deloulme (), Sylvie Gory-Fauré, Franck Mauconduit, Sophie Chauvet, Julie Jonckheere, Benoit Boulan, Erik Mire, Jing Xue, Marion Jany, Caroline Maucler, Agathe A. Deparis, Olivier Montigon, Alexia Daoust, Emmanuel L. Barbier, Christophe Bosc, Nicole Deglon, Jacques Brocard, Eric Denarier, Isabelle Le Brun, Karin Pernet-Gallay, Isabelle Vilgrain, Phillip J. Robinson, Hana Lahrech, Fanny Mann and Annie Andrieux ()
Additional contact information
Jean-Christophe Deloulme: INSERM
Sylvie Gory-Fauré: INSERM
Franck Mauconduit: INSERM
Sophie Chauvet: Aix-Marseille Université, CNRS
Julie Jonckheere: INSERM
Benoit Boulan: INSERM
Erik Mire: Aix-Marseille Université, CNRS
Jing Xue: Cell Signalling Unit, Children’s Medical Research Institute, University of Sydney, Wentworthville
Marion Jany: INSERM
Caroline Maucler: INSERM
Agathe A. Deparis: INSERM
Olivier Montigon: INSERM
Alexia Daoust: INSERM
Emmanuel L. Barbier: INSERM
Christophe Bosc: INSERM
Nicole Deglon: Lausanne University Hospital (CHUV), Laboratory of Cellular and Molecular Neurotherapies (LCMN)
Jacques Brocard: INSERM
Eric Denarier: INSERM
Isabelle Le Brun: Univ. Grenoble Alpes, Grenoble Institut Neurosciences
Karin Pernet-Gallay: INSERM
Isabelle Vilgrain: Univ. Grenoble Alpes, Grenoble Institut Neurosciences
Phillip J. Robinson: Cell Signalling Unit, Children’s Medical Research Institute, University of Sydney, Wentworthville
Hana Lahrech: INSERM
Fanny Mann: Aix-Marseille Université, CNRS
Annie Andrieux: INSERM

Nature Communications, 2015, vol. 6, issue 1, 1-16

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms8246

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