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

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...

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Detalles Bibliográficos
Autores: Peris, Leticia, Bisbal, Mariano, Martínez Hernández, José, Saoudi, Yasmina, Jonckheere, Julie, Rolland, Marta, Sebastien, Muriel, Brocard, Jacques, Denarier, Eric, Bosc, Christophe, Guerin, Christophe, Gory-Fauré, Sylvie, Deloulme, Jean Christophe, Lanté, Fabien, Arnal, Isabelle, Buisson, Alain, Goldberg, Yves, Blanchoin, Laurent
Tipo de recurso: artículo
Fecha de publicación:2018
País:España
Institución:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/30758
Acceso en línea:http://hdl.handle.net/10810/30758
Access Level:acceso abierto
Palabra clave:long-term potentiation
bundles f-actin
synaptic plasticity
dynamic microtubule
binding
tau
growth
stop
phosphorylation
depolymerization
Descripción
Sumario: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.

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