First evidence of the Fast axonal transport of the proteasome complex fast axonal transport and membrane interactioncomplex depends onmediated by molecular motors and membrane interaction

OTERO MG; FALZONE T

Huerta Grande, Cordoba

Congreso; XXIX congreso de la SAN; 2014

SAN

Local protein degradation by the ubiquitin-proteasome system in neurons depends on the correct positioning of this complex ?machinery?. Abnormal protein degradation is suggested as an early event in Alzheimer disease (AD), linking protein degradation impairments with proteasome transport defects. However, the properties of proteasomes axonal transport remains unknown. In order to demonstrate that proteasomes are being transported in vivo, we performed a sciatic nerve ligation showing proteasome accumulation at both sides of the nerve. To reveal proteasome axonal transport dynamics we used live-cell imaging experiments in primary hippocampal neurons. To understand whether proteasome movement depends on molecular motors we used a shRNA to knock down molecular motor expression. To assess whether proteasomes associate with intracellular membranes we performed a botton loaded sucrose density gradient. Finally, by live imaging in dual color channel we showed that fast and actively transported proteasome associates to different vesicles and membranes organelles to reach distant locations. Taken together our results demonstrate for the first time that the proteasome complex is transported throughout axons using different processive molecular motors and ?Hitch-hiking? on multiple vesicles, this mechanism assure the correct transport and localization of this degradative machinery that when  impaired could lead to local aberrant protein accumulation such as those observed in AD.