Because of their functional polarity and elongated morphologies， microtubule-based transport of proteins and organelles is critical for normal neuronal function. The proteasome is required throughout the neuron for the highly regulated degradation of a broad set of protein targets whose functions underlie key physiological responses， including synaptic plasticity and axonal degeneration. Molecularly， the relationship between proteasome transport and the transport of the targets of proteasomes is unclear. The dynein motor complex is required for the microtubule-based motility of numerous proteins and organelles in neurons. Here， we demonstrate that microtubule-based transport of proteasomes within the ne... More
Because of their functional polarity and elongated morphologies， microtubule-based transport of proteins and organelles is critical for normal neuronal function. The proteasome is required throughout the neuron for the highly regulated degradation of a broad set of protein targets whose functions underlie key physiological responses， including synaptic plasticity and axonal degeneration. Molecularly， the relationship between proteasome transport and the transport of the targets of proteasomes is unclear. The dynein motor complex is required for the microtubule-based motility of numerous proteins and organelles in neurons. Here， we demonstrate that microtubule-based transport of proteasomes within the neuron in utilizes a different dynein light chain to that used by synaptic proteins. Live imaging of proteasomes and synaptic vesicle proteins in axons and synapses finds that these cargoes traffic independently， and that proteasomes exhibit significantly reduced retrograde transport velocities compared to those of synaptic vesicle proteins. Genetic and biochemical analyses reveals that the homolog of the LC8 dynein light chains (mammalian DYNLL1 and DYNLL2)， called Cut up， binds proteasomes and functions specifically during their transport. These data support the model that Cut up functions to specify the dynein-mediated transport of neuronal proteasomes.
