IBCN   20355
INSTITUTO DE BIOLOGIA CELULAR Y NEUROCIENCIA "PROFESOR EDUARDO DE ROBERTIS"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Kinesin1 is required for axonal pathfinding and cannabinoid induced axonal development by mediating the axonal transport of CB1 r
Autor/es:
CROMBERG, LUCAS ENEAS; FALZONE, TOMÁS L.; MARIA GABRIELA OTERO; DIEGO GELMAN; TRINIDAD M.M. SAEZ; MATIAS ALLOATTI
Lugar:
Buenos Aires
Reunión:
Congreso; FALAN Congress 2016; 2016
Institución organizadora:
FALAN
Resumen:
During development, axonal navigation through the intricate architecture of the brain depends on the proper presentation and positioning of guidance receptors.Receptors for axonal guidance are localized in growth cones, where they are activated by attractive or repulsive guidance cues resulting in axonal pathfinding decisions. However, little is known about the crucial mechanisms controlling the trafficking of these receptors involved in neural circuitswiring. The endocannabinoid (eCB) system has been identified as an important regulator of axonal pathfinding. eCB mediate the directional turning of axons by activating type 1 cannabinoid receptor (CB1R) in axonal growth cones. To test the whether CB1R delivery to the growth cone depends on kinesin-1 mediated axonal transport, we used mice lacking the kinesin light chain 1 (klc1) subunit of the anterograde motor kinesin-1. We performed L1-NCAM staining and axon-tracing experiments in developing klc1-/- brains and found pathfinding defects in axonal tracts. Using live imaging of fluorescent CB1R tagged vesiclesin klc1-/- neurons, we revealed the dependency of Klc1 in CB1R transport towards the axonal growth cone. Next, we demonstrated that klc1 is required for the correct axonal growth cone remodeling and outgrowth-induced by CB1R agonist and antagonist. Altogether, our results suggest that kinesin-1-mediated axonal transport of CB1R is required for a normal eCB signaling and is also required for proper axonal pathfinding