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J Cell Biol. 2012 Feb 20;196(4):407-17. doi: 10.1083/jcb.201106120. Epub 2012 Feb 13.

Autophagosomes initiate distally and mature during transport toward the cell soma in primary neurons.

Author information

1
Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Abstract

Autophagy is an essential cellular degradation pathway in neurons; defects in autophagy are sufficient to induce neurodegeneration. In this paper, we investigate autophagosome dynamics in primary dorsal root ganglion neurons. Autophagosome biogenesis occurs distally in a constitutive process at the neurite tip. Autophagosomes initially move bidirectionally and then switch to unidirectional, processive movement toward the cell soma driven by dynein. Autophagosomes copurify with anterograde and retrograde motors, suggesting that the activity of bound kinesin motors is effectively down-regulated to yield robust retrograde motility driven by dynein. Both organelle and soluble cargoes are internalized into autophagosomes, including mitochondria and ubiquitin. As autophagosomes move distally to proximally, they undergo maturation and become increasingly acidified, consistent with the formation of an autolysosomal compartment that may more efficiently degrade cargo. This maturation is accompanied by a switch to bidirectional motility characteristic of lysosomes. Together, autophagosome biogenesis and maturation in primary neurons is a constitutive process that is spatially and temporally regulated along the axon.

PMID:
22331844
PMCID:
PMC3283992
DOI:
10.1083/jcb.201106120
[Indexed for MEDLINE]
Free PMC Article

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