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

BISBAL M; PERIS L.,SEGGIO M., RUSH R., GORY-FAURÉ S., BOSC C., BUISSON A., DELPHIN C., ANDRIEUX A.

Puerto Natales

Workshop; EMBO Workshop: Current advances in membrane trafficking: Implications for polarity and diseases; 2014

EMBO

Microtubule associated protein MAP6 (also known as STOP) initially have been identified as a structural MAP crucially involved in neuronal microtubule stability properties. The MAP6-deficient mice exhibited severe alterations of brain functions with neurotransmission anomalies and sensorimotor gating impairment, associated with severe behavioural deficits that react positively to antipsychotic drugs after chronic treatments. The MAP6-null mice also show global reduction of the brain mass, associated with widespread deficits in axonal extensions, whereas the number of neurons seems unaffected, an observation similar to post-mortem observation in patients with schizophrenia. However little is known about the biological function and the cellular targets of MAP6 protein in neurons. In this study, we have used a combination of biochemical and molecular biology techniques to demonstrate a novel function of MAP6 in spinogenesis. We show that MAP6-null mice have a decreased dendritic spines density in hippocampal cultured neurons as well as in neurons at the layer V in the prefrontal cortex of fixed brain slices, an effect that can be rescued by the overexpression of wild-type MAP6. Besides, we find that the central repeat domain (Mc domain) of MAP6 directly interacts with actin cytoskeleton and this domain is important for the localization of MAP6 in dendritic spines and regulates the function of MAP6 in dendritic spines formation and maturation. Taken together, our results suggest a novel and important role for MAP6 in the formation and maturation of dendritic spines, possibly through the regulation of the actin cytoskeleton.