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Microtubule-associated protein 6 mediates neuronal connectivity through Semaphorin 3E-dependent signalling for axonal growth
- Source :
- Nature Communications, Nature Communications, Nature Publishing Group, 2015, 6 (1), Nature Communications, 2015, 6 (1), Nature Communications, Nature Publishing Group, 2015, 6, pp.7246. ⟨10.1038/ncomms8246⟩, HAL, Nature Communications, vol. 6, pp. 7246, Nature Communications, 2015, 6, pp.7246. ⟨10.1038/ncomms8246⟩
- Publication Year :
- 2015
- Publisher :
- HAL CCSD, 2015.
-
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.<br />Loss of the structural microtubule-associated protein 6 (MAP6) leads to neuronal differentiation defects that are independent of MAP6's microtubule-binding properties. Here the authors establish a functional link between MAP6 and Semaphorin 3E signalling for proper formation of the fornix of the brain.
- Subjects :
- [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
[SDV]Life Sciences [q-bio]
Fornix, Brain
Semaphorins
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
Microtubules
Article
src Homology Domains
Animals
Axons/metabolism
Brain/metabolism
Brain/pathology
Diffusion Tensor Imaging
Fornix, Brain/embryology
Fornix, Brain/metabolism
Glycoproteins/metabolism
HEK293 Cells
Humans
Magnetic Resonance Imaging
Membrane Proteins/metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Microscopy, Electron
Microtubule-Associated Proteins/genetics
Neural Pathways/embryology
Neural Pathways/metabolism
Neurites/metabolism
Neuroanatomical Tract-Tracing Techniques
Neurons/metabolism
Organ Size
Neural Pathways
Neurites
[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM]
[SDV.BDD]Life Sciences [q-bio]/Development Biology
ComputingMilieux_MISCELLANEOUS
Glycoproteins
Neurons
Brain
Membrane Proteins
Development of the nervous system
[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology
Axons
Cytoskeletal proteins
nervous system
Microtubule-Associated Proteins
Cell signalling
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Database :
- OpenAIRE
- Journal :
- Nature Communications, Nature Communications, Nature Publishing Group, 2015, 6 (1), Nature Communications, 2015, 6 (1), Nature Communications, Nature Publishing Group, 2015, 6, pp.7246. ⟨10.1038/ncomms8246⟩, HAL, Nature Communications, vol. 6, pp. 7246, Nature Communications, 2015, 6, pp.7246. ⟨10.1038/ncomms8246⟩
- Accession number :
- edsair.pmid.dedup....b4f1f38468018419c2a4848c280c48b7