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KIF1A/UNC-104 transports ATG-9 to regulate neurodevelopment and autophagy at synapses

Andrea K. H. Stavoe, Sarah E. Hill, Daniel A. Colón-Ramos
doi: https://doi.org/10.1101/057166
Andrea K. H. Stavoe
1Program in Cellular Neuroscience, Neurodegeneration and Repair, Department of Cell Biology, Yale University School of Medicine, P.O. Box 9812, New Haven, CT, 06536-0812, USA
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Sarah E. Hill
1Program in Cellular Neuroscience, Neurodegeneration and Repair, Department of Cell Biology, Yale University School of Medicine, P.O. Box 9812, New Haven, CT, 06536-0812, USA
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Daniel A. Colón-Ramos
1Program in Cellular Neuroscience, Neurodegeneration and Repair, Department of Cell Biology, Yale University School of Medicine, P.O. Box 9812, New Haven, CT, 06536-0812, USA
2Instituto de Neurobiologia, Recinto de Ciencias Medicas, Universidad de Puerto Rico, 201 Blvd del Valle, San Juan, Puerto Rico
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  • For correspondence: daniel.colon-ramos@yale.edu
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SUMMARY

Autophagy is a cellular degradation process essential for neuronal development and survival. Neurons are highly polarized cells in which autophagosome biogenesis is spatially compartmentalized. The mechanisms and physiological importance of this spatial compartmentalization of autophagy in the neuronal development of living animals are not well understood. Here we determine that, in C. elegans neurons, autophagosomes form near synapses and are required for neurodevelopment. We first determined, through unbiased genetic screens and systematic genetic analyses, that autophagy is required cell-autonomously for presynaptic assembly and for axon outgrowth dynamics in specific neurons. We observe autophagosomes in the axon near synapses, and this localization depends on the synaptic vesicle kinesin, KIF1A/UNC-104. KIF1A/UNC-104 coordinates localized autophagosome formation by regulating the transport of the integral membrane autophagy protein, ATG-9. Our findings indicate that autophagy is spatially regulated in neurons through the transport of ATG-9 by KIF1A/UNC-104 to regulate neurodevelopment.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted June 05, 2016.
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KIF1A/UNC-104 transports ATG-9 to regulate neurodevelopment and autophagy at synapses
Andrea K. H. Stavoe, Sarah E. Hill, Daniel A. Colón-Ramos
bioRxiv 057166; doi: https://doi.org/10.1101/057166
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KIF1A/UNC-104 transports ATG-9 to regulate neurodevelopment and autophagy at synapses
Andrea K. H. Stavoe, Sarah E. Hill, Daniel A. Colón-Ramos
bioRxiv 057166; doi: https://doi.org/10.1101/057166

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