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Nat Commun. 2015 Jun 3;6:7246. doi: 10.1038/ncomms8246.

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

Author information

1
1] INSERM, U836, F-38000 Grenoble, France [2] Univ. Grenoble Alpes, Grenoble Institut Neurosciences, F-38000 Grenoble, France.
2
Aix-Marseille Université, CNRS, IBDM UMR 7288, 13288 Marseille, France.
3
Cell Signalling Unit, Children's Medical Research Institute, University of Sydney, Wentworthville, New South Wales 2145, Australia.
4
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.
5
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.
6
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.
7
1] Univ. Grenoble Alpes, Grenoble Institut Neurosciences, F-38000 Grenoble, France [2] INSERM, U1036, 38054 Grenoble, France [3] CEA, iRTSV, F-38000 Grenoble, France.
8
1] Univ. Grenoble Alpes, Grenoble Institut Neurosciences, F-38000 Grenoble, France [2] INSERM, U1036, 38054 Grenoble, France [3] INSERM, U1036, 38054 Grenoble, France.
9
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.

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.

PMID:
26037503
PMCID:
PMC4468860
DOI:
10.1038/ncomms8246
[Indexed for MEDLINE]
Free PMC Article

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