University of Cambridge > Talks.cam > MRC LMB Seminar list > Long-distance organelle transport in the neuron: mechanisms of motor engagement and motor coordination

Long-distance organelle transport in the neuron: mechanisms of motor engagement and motor coordination

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The long distance transport of organelles along the axon is driven by the microtubule motors kinesin and cytoplasmic dynein. This transport is required to maintain the extended axons of neurons; mutations in either the motors or their activators and adaptors are sufficient to cause neurodegeneration. We are focusing on the mechanisms regulating molecular motor function during transport along the axon. Active coordination of opposing motors is essential, as many vesicular cargos undergoing transport along microtubules in the axon have both plus end-directed kinesins and minus-end directed dynein motors bound simultaneously. We are investigating the role of scaffolding proteins including JIP1 and Huntingtin in coordinating the activities of kinesin and dynein motors, allowing for the processive and efficient long-range motility of diverse cargos including APP -positive vesicles and autophagosomes. During retrograde transport, efficient initiation of vesicular transport requires the dynein activator dynactin as well as microtubule plus end-binding proteins including EB1 . Together, data from both live cell imaging and in vitro reconstitution experiments with single molecule resolution can be used to build detailed models providing mechanistic insight into the regulation of motor coordination and motor engagement during axonal transport in neurons.

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