IBCN   20355
INSTITUTO DE BIOLOGIA CELULAR Y NEUROCIENCIA "PROFESOR EDUARDO DE ROBERTIS"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Kinesin-1 is required for cannabinoid-induced axonal development through the axonal transport of CB1 receptor
Autor/es:
CROMBERG L; ALLOATTI M; FALZONE T; SAEZ T; GELMAN D
Lugar:
San Diego
Reunión:
Congreso; Society for Neuroscience; 2016
Institución organizadora:
Society for Neuroscience
Resumen:
During development, axons navigation through the intricate architecture of the brain depends on the proper presentation and positioning of guidance receptors for the correct reading of external clues. Receptors for axonal growth and guidance are shifted to axons and 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 proper trafficking of these receptors for the wiring of neural circuits. The endocannabinoid (eCB) system has been identified as an important regulator of axonal outgrowth and pathfinding. eCBs mediate the motility and directional turning of axons by activating type 1 cannabinoid receptor (CB1R) in the growth cone. Although cargo delivery mediated by molecular motors is essential in developing neurons, the mechanism underlying the directional axonal transport of CB1R remains basically unknown. To test the hypothesis that CB1R function depends on kinesin-1 mediated anterograde delivery for proper axonal guidance, we use mice lacking the kinesin light chain 1 (klc1) subunit of the anterograde motor kinesin-1. Here, we showed several pathfinding defects in corticothalamic and thalamocrtical axonal tracts in developing klc1 knockout brain, resembling CB1 knockout mice phenotypes. To unravel the axonal transport properties of CB1R and test whether kinesin-1 molecular motor mediates the transport of CB1R we used live imaging of fluorescent CB1R tagged vesicles in wildtype and klc1-/- neurons. Interestingly, we revealed the dependency of Kinesin-1 motor for normal CB1R dynamics and positioning towards growth cone. Finally, we demonstrated that kinesin-1 is required for correct growth cone remodeling and axonal 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 in axonal pathfinding.