IBCN   20355
INSTITUTO DE BIOLOGIA CELULAR Y NEUROCIENCIA "PROFESOR EDUARDO DE ROBERTIS"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
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
Autor/es:
OTERO MG; FALZONE T
Lugar:
Huerta Grande, Cordoba
Reunión:
Congreso; XXIX congreso de la SAN; 2014
Institución organizadora:
SAN
Resumen:
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.