Autophagosome assembly and cargo capture in the distal axon

Autophagy is an essential lysosomal degradation pathway in neurons, yet the basic mechanisms involved are poorly understood. Here, we discuss our recent study in which we define autophagosome dynamics in primary neurons. We find that autophagosomes initiate at the distal tip of the axon in primary neurons and undergo retrograde transport toward the cell soma. As they move distally to proximally along the axon, autophagosomes mature and become increasingly acidified, consistent with the formation of an autolysosomal compartment that may more effectively catalyze the degradation of enveloped cargo. Our findings suggest that autophagosome biogenesis and maturation is a constitutive process in primary neurons that is temporally and spatially regulated along the axon.