A key function for microtubule-associated-protein 6 in activity-dependent stabilisation of actin filaments in dendritic spines

Leticia Peris (), Mariano Bisbal (), José Martinez-Hernandez, Yasmina Saoudi, Julie Jonckheere, Marta Rolland, Muriel Sebastien, Jacques Brocard, Eric Denarier, Christophe Bosc, Christophe Guerin, Sylvie Gory-Fauré, Jean Christophe Deloulme, Fabien Lanté, Isabelle Arnal, Alain Buisson, Yves Goldberg, Laurent Blanchoin, Christian Delphin and Annie Andrieux ()
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Leticia Peris: Univ. Grenoble Alpes
Mariano Bisbal: Univ. Grenoble Alpes
José Martinez-Hernandez: Univ. Grenoble Alpes
Yasmina Saoudi: Univ. Grenoble Alpes
Julie Jonckheere: Univ. Grenoble Alpes
Marta Rolland: Univ. Grenoble Alpes
Muriel Sebastien: Univ. Grenoble Alpes
Jacques Brocard: Univ. Grenoble Alpes
Eric Denarier: Univ. Grenoble Alpes
Christophe Bosc: Univ. Grenoble Alpes
Christophe Guerin: Univ. Grenoble-Alpes
Sylvie Gory-Fauré: Univ. Grenoble Alpes
Jean Christophe Deloulme: Univ. Grenoble Alpes
Fabien Lanté: Univ. Grenoble Alpes
Isabelle Arnal: Univ. Grenoble Alpes
Alain Buisson: Univ. Grenoble Alpes
Yves Goldberg: Univ. Grenoble Alpes
Laurent Blanchoin: Univ. Grenoble-Alpes
Christian Delphin: Univ. Grenoble Alpes
Annie Andrieux: Univ. Grenoble Alpes

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: Abstract Emerging evidence indicates that microtubule-associated proteins (MAPs) are implicated in synaptic function; in particular, mice deficient for MAP6 exhibit striking deficits in plasticity and cognition. How MAP6 connects to plasticity mechanisms is unclear. Here, we address the possible role of this protein in dendritic spines. We find that in MAP6-deficient cortical and hippocampal neurons, maintenance of mature spines is impaired, and can be restored by expressing a stretch of the MAP6 sequence called Mc modules. Mc modules directly bind actin filaments and mediate activity-dependent stabilisation of F-actin in dendritic spines, a key event of synaptic plasticity. In vitro, Mc modules enhance actin filament nucleation and promote the formation of stable, highly ordered filament bundles. Activity-induced phosphorylation of MAP6 likely controls its transfer to the spine cytoskeleton. These results provide a molecular explanation for the role of MAP6 in cognition, enlightening the connection between cytoskeletal dysfunction, synaptic impairment and neuropsychiatric illnesses.

Date: 2018
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DOI: 10.1038/s41467-018-05869-z

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