INVESTIGADORES
BISBAL mariano
congresos y reuniones científicas
Título:
Microtubule-associated protein 6 (MAP6/STOP) is required for the formation and maturation of dendritic spines
Autor/es:
BISBAL M; PERIS L.,SEGGIO M., RUSH R., GORY-FAURÉ S., BOSC C., BUISSON A., DELPHIN C., ANDRIEUX A.
Lugar:
Puerto Natales
Reunión:
Workshop; EMBO Workshop: Current advances in membrane trafficking: Implications for polarity and diseases; 2014
Institución organizadora:
EMBO
Resumen:
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.