Genetic evidence for the role of Glycogen synthase kinase-3beta in axonal transport
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Within axons, molecular motors transport essential components, including signaling proteins, neuroprotective molecules, vesicular components, which are required for neuronal growth and viability. Recent studies show that defects in axonal transport pathways may contribute to the initiation of chronic neurodegenerative diseases. Many levels of control and regulation must exist for proper anterograde and retrograde intracellular transport of vital proteins. However little is known about these regulatory mechanisms during axonal transport. Here we show using Drosophila genetics that glycogen synthase kinase-3β (GSK-3β) plays a vital role in axonal transport. We find that inactive GSK-3β but not active GSK-3β cause axonal transport defects. Axonal defects induced by inactive GSK-3β are enhanced by reduction of presenilin (PS), a gene involved in Alzheimer's disease (AD). We also found that GSK-3β activity can influence both kinesin and dynein motors. Our findings suggest that GSK-3β is required for normal motor function and that PS can affect axonal transport by regulating GSK-3β activity. Thus, molecular motor regulatory problems induced by loss of PS and decreased GSK-3β activity may critically influence the initiation of degeneration.