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

PERIS, LETICIA; SAOUDI, YASMINA; SEBASTIEN, MURIEL; BOSC, CHRISTOPHE; DELOULME, JEAN CHRISTOPHE; BUISSON, ALAIN; DELPHIN, CHRISTIAN; BISBAL, MARIANO; JONCKHEERE, JULIE; BROCARD, JACQUES; GUERIN, CHRISTOPHE; LANTÉ, FABIEN; GOLDBERG, YVES; ANDRIEUX, ANNIE; MARTINEZ-HERNANDEZ, JOSÉ; ROLLAND, MARTA; DENARIER, ERIC; GORY-FAURÉ, SYLVIE; ARNAL, ISABELLE; BLANCHOIN, LAURENT

NATURE COMMUNICATIONS

Nature Publishing Group

Año: 2018 vol. 9

2041-1723

Emerging evidence indicates that microtubule-associated proteins (MAPs) are implicated insynaptic function; in particular, mice deficient for MAP6 exhibit striking deficits in plasticityand cognition. How MAP6 connects to plasticity mechanisms is unclear. Here, we addressthe possible role of this protein in dendritic spines. We find that in MAP6-deficient corticaland hippocampal neurons, maintenance of mature spines is impaired, and can be restored byexpressing a stretch of the MAP6 sequence called Mc modules. Mc modules directly bindactin filaments and mediate activity-dependent stabilisation of F-actin in dendritic spines, akey event of synaptic plasticity. In vitro, Mc modules enhance actin filament nucleation andpromote the formation of stable, highly ordered filament bundles. Activity-induced phosphorylationof MAP6 likely controls its transfer to the spine cytoskeleton. These resultsprovide a molecular explanation for the role of MAP6 in cognition, enlightening the connectionbetween cytoskeletal dysfunction, synaptic impairment and neuropsychiatricillnesses.