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Updated: May 23, 2025

Expanding the Toolkit for In Vivo Imaging of Axonal Transport
Published on: December 23, 2021
Sorting trash from treasure: Separate pathways for autophagy and endocytic trafficking in axons
Vineet Vinay Kulkarni1, Sandra Maday1
1Department of Neuroscience, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Abstract:
Macroautophagy (hereafter autophagy) and endocytic trafficking are key pathways in neuronal axons that regulate the composition and integrity of the axonal proteome. These pathways have similar trafficking itineraries; however, the extent of their cross-talk remains incompletely understood. Our recent work demonstrates that under physiological conditions, axonal autophagy and endocytic pathways are separate and exhibit distinct rates of organelle maturation. Strikingly, overexpression of pathogenic α-synuclein disrupts the segregation between these pathways by merging autophagosomes and endosomes generated in the distal axon. These results raise the possibility that precocious degradation of endocytosed cargo via misrouting into lysosome-destined autophagosomes may contribute to neuronal dysfunction in Parkinson disease and related α-synucleinopathies.
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