Aberrant accumulation of AVs in snapin-deficient neuronal processes. (A–D) TEM showing aberrant accumulation of double-membrane AVs along neurites (B) and at presynaptic terminals (D) of snapin^−/− cortical neurons at DIV14. Red arrows indicate AV-like structures, which are not readily observed in WT neurons. Blue arrows point to synaptic active zones. Images were representative from 35–50 electron micrographs from three pairs of mice. Bars, 100 nm. (E) A model of LE-loaded dynein–snapin complex driving AV for retrograde trafficking along axons. (E′) Autophagosomes (green) at distal axons acquire the dynein motor complex from LEs (red) upon their fusion into amphisomes. Therefore, dynein–snapin complexes mediate amphisomes, but not autophagosomes, for long-distance retrograde trafficking to the soma, where mature acidic lysosomes are mainly located.