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Dev Cell. 2016 Jul 25;38(2):171-85. doi: 10.1016/j.devcel.2016.06.012. Epub 2016 Jul 7.

KIF1A/UNC-104 Transports ATG-9 to Regulate Neurodevelopment and Autophagy at Synapses.

Author information

1
Program in Cellular Neuroscience, Neurodegeneration and Repair, Departments of Cell Biology and Neuroscience, Yale University School of Medicine, 295 Congress Avenue, BCMM 436B, New Haven, CT 06536-0812, USA.
2
Center for C. elegans Anatomy, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
3
Program in Cellular Neuroscience, Neurodegeneration and Repair, Departments of Cell Biology and Neuroscience, Yale University School of Medicine, 295 Congress Avenue, BCMM 436B, New Haven, CT 06536-0812, USA; Instituto de Neurobiología, Recinto de Ciencias Médicas, Universidad de Puerto Rico, 201 Boulevard del Valle, San Juan 00901, Puerto Rico. Electronic address: daniel.colon-ramos@yale.edu.

Abstract

Autophagy is a cellular degradation process important 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 Caenorhabditis elegans neurons, autophagosomes form near synapses and are required for neurodevelopment. We first determine, 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 autophagosome biogenesis 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.

PMID:
27396362
PMCID:
PMC4961624
DOI:
10.1016/j.devcel.2016.06.012
[Indexed for MEDLINE]
Free PMC Article

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