摘要
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Summary
p150Glued is the major subunit of dynactin, a complex that functions with dynein in minus-end-directed microtubule transport. Mutations within the p150Glued CAP-Gly microtubule-binding domain cause neurodegenerative diseases through an unclear mechanism. A p150Glued motor neuron degenerative disease-associated mutation introduced into the Drosophila Glued locus generates a partial loss-of-function allele (GlG38S) with impaired neurotransmitter release and adult-onset locomotor dysfunction. Disruption of the p150Glued CAP-Gly domain in neurons causes a specific disruption of vesicle trafficking at聽terminal boutons (TBs), the distal-most ends of synapses. GlG38S larvae accumulate endosomes along with dynein and kinesin motor proteins within swollen TBs, and genetic analyses show that kinesin and p150Glued function cooperatively at TBs to coordinate transport. Therefore, the p150Glued CAP-Gly domain regulates dynein-mediated retrograde transport at synaptic termini, and this function of dynactin is disrupted by a mutation that causes motor聽neuron disease.
