Proteasomes interact with intracellular membrane organelles for their movement in axons.

*M. G. OTERO, M. ALLOATTI, L. E. CROMBERG, V. POZO DEVOTO, T. L. FALZONE

San Diego

Congreso; Neuroscience 2013- Society for Neuroscience; 2013

Abstract: (Aprobado para su exposicion) Local protein degradation by the ubiquitin-proteasome system (UPS) in neurons is involved in the development, maintenance and plasticity of neuronal projections and synapses, which depends in the correct delivery and positioning of the proteasome degradative machinery. Protein turnover by the UPS involves the identification and tagging of targets with a poly-ubiquitin chain as the signal for specific degradation by the proteasome complex. The 26S proteasome barrel is assembled by the interaction of the 20S catalytic core composed of four rings of α and β subunits with the 19S regulatory particle. Cargos transported along axons can interact directly or indirectly with the molecular motors that drive the movement of protein complexes or vesicles to distant neuronal locations. Abnormal protein aggregation and axonal deposition are suggested as common local features in neuronal dysfunction observed as swellings, linking protein degradation impairments with axonal transport defects. Although the proteasomes are thought to be delivered to synapses and an interaction of the proteasome with the motor machinery have been suggested through the proteasome interacting protein ECM29, little is known about the axonal transport dynamics of the proteasome and the compartment used for movement. Here, we report the fast and motor dependent axonal transport of the proteasome complex, in addition to the rapid impairment of axonal transport dynamics of selective cargos when proteasome degradation is inhibited. Using double channel live imaging recordings in primary hippocampal neurons we showed the fast and processive movement of particulate anterograde and retrograde fluorescent proteasomes associated with different types of intracellular membranes. We then tested whether the proteasome complex relies on trans golgi vesicles, endo-lysosome vesicles and organelles for their movement in axons. In addition, we set up our system to measure the rapid changes induced in axonal transport dynamics of different cargos when proteasome dependent degradation is inhibited. Our results establish a novel axonal transport mechanism of assembled cytoplasmic proteasome complexes mediated via association with intracellular membrane organelles and suggest that proteasome defects can act as a negative regulator of the transport of other cargos.