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bioRxiv · 10.1101/287144

Retrograde Transport and ATG-4.2-Mediated Maturation Cooperate to Remove Autophagosomes from the Synapse

Hill, S. E.·Colon-Ramos, D.
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Abstract

Autophagy is spatially compartmentalized in neurons, with autophagosome biogenesis occurring in the axon and degradation in the cell body. The mechanisms that coordinate autophagosome formation, trafficking and degradation across the polarized structure of the neuron are not well understood. Here we use genetic screens and in vivo imaging in single neurons of C. elegans to demonstrate that specific steps of autophagy are differentially required in distinct subcellular compartments of the neuron. We demonstrate that completion of autophagosome biogenesis and closure at the synapse are necessary for dynein-mediated retrograde transport. We uncover a role for UNC-16/JIP3/Sunday Driver in facilitating autophagosome retrograde transport. Through forward genetic screens we then determine that autophagosome maturation and degradation in the cell body depend on removal of LGG-1/Atg8/GABARAP from autophagosomes by the protease ATG-4.2. Our studies reveal that regulation of distinct ATG4 proteases contributes to the coordination of autophagy across subcellular regions of the neuron.\n\nHIGHLIGHTS and eTOC BlurbO_LIAutophagosome closure, but not maturation, occurs locally at presynaptic sites\nC_LIO_LIRetrograde transport of autophagosomes requires the motor adaptor UNC-16/JIP3\nC_LIO_LIThe autophagy protease ATG-4.2, but not the related ATG-4.1, is required for autophagosome maturation and degradation\nC_LIO_LIDefects in retrograde transport and maturation genetically interact and enhance accumulation of autophagosomes in presynaptic regions\nC_LI

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Hill, S. E., Colon-Ramos, D.. 2018-03-22. Retrograde Transport and ATG-4.2-Mediated Maturation Cooperate to Remove Autophagosomes from the Synapse. https://doi.org/10.1101/287144

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