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Significance Anterograde axonal transport supplies organelles and protein complexes throughout axonal processes to support neuronal morphology and function. It has been observed that reduced anterograde axonal transport is associated with neuronal diseases. In contrast, here we show that particular disease-associated mutations in KIF1A, an anterograde axonal motor for synaptic vesicle precursors, induce hyperactivation of KIF1A motor activity and increased axonal transport of synaptic vesicle precursors. Our results advance the existing knowledge of the regulation of motor proteins in axonal transport and provide insight into the cell biology of motor neuron diseases.

Disease-associated mutations hyperactivate KIF1A motility and anterograde axonal transport of synaptic vesicle precursors