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

•The autophagy pathway is required for presynaptic assembly in vivo•The autophagy pathway acts cell autonomously and in specific neurons in development•Autophagosome biogenesis occurs in compartmentalized axonal regions near synapses•The synaptic vesicle kinesin UNC-104/KIF1A transports ATG-9 to presynaptic sites

SummaryAutophagy 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.

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