Microtubule-associated protein 6 (MAP6/STOP) is required for the formation and maturation of dendritic spines

BISBAL M; PERIS L; BATANDIER C

Puerto Varas

Workshop; EMBO Workshop: Emerging Concepts on Neuronal Cytoskeleton.; 2015

EMBO

Microtubule associated protein MAP6 (also known as STOP) initially has been identified asa structural MAP crucially involved in neuronal microtubule stability. The MAP6-null miceexhibited severe alterations of brain functions with neurotransmission anomalies andsensorimotor gating impairment, associated with severe behavioral deficits that reactpositively to antipsychotic drugs after chronic treatments leading to a schizophrenic-likephenotype. The MAP6-null mice also show synaptic defects affecting both short-term andlong-term synaptic plasticity. However little is known about the biological function and thecellular targets of MAP6 protein in neurons. In this study, we have used a combination ofbiochemical, molecular and cell biology techniques to demonstrate a novel function ofMAP6 in synaptic plasticity. We show that MAP6-null mice have a decreased dendriticspines density in neurons at layer V in the prefrontal cortex of fixed brain slices as well asin hippocampal cultured neurons, that can be rescued by the overexpression of wild-typeMAP6. Besides, we find that the central repeat domain (Mc domain) of MAP6 colocalizewith actin cytoskeleton in growth cones and dendritic spines and we show that MAP6directly interacts with actin cytoskeleton through this domain using acceptorphotobleaching FRET and biochemical analysis of purified MAP6. Finally, usingFluorescence Recovery After Photobleaching (FRAP) analysis we revealed an activitydependentregulation of actin dynamics by Mc domains in dendritic spines of livingneurons. Taken together, our results suggest a novel and important role for MAP6 in theformation and maturation of dendritic spines through the regulation of the actincytoskeleton.