Autophagosomes gain the dynein motor complexes they need to move away from axonal terminals by fusing with late endosomes, Cheng et al. reveal.
During autophagy, autophagosomes engulf cytoplasmic components and deliver them to lysosomes for degradation. In neurons, mature acidic lysosomes are enriched in the cell body, so autophagosomes formed at the distal ends of axons must be transported back to the soma by the motor protein dynein. How dynein is recruited to autophagosomes is unknown, however.
Cheng et al. found that the majority of axonal autophagosomes fuse with late endosomes to form intermediate organelles known as amphisomes. Unlike autophagosomes, but similar to late endosomes, amphisomes were associated with dynein and moved along axons toward the cell body. This suggested that autophagosomes might become mobile by fusing with late endosomes and sharing their complement of dynein motors. Accordingly, blocking dynein’s recruitment to late endosomes by inhibiting the adaptor protein snapin impaired the movement of amphisomes toward the cell body, and reducing the ability of autophagosomes to fuse with late endosomes caused immobile autophagic compartments to accumulate in axon terminals.
Live imaging revealed that autophagosomes can fuse with late endosomes and move retrogradely along axons within one minute of their formation. Senior author Zu-Hang Sheng says that similar events occur much more slowly in nonneuronal cells. He therefore wants to investigate whether local calcium levels speed up autophagosome fusion in synaptic terminals.
Text by Ben Short