RRC ID 30832
Author Maday S, Holzbaur EL.
Title Autophagosome biogenesis in primary neurons follows an ordered and spatially regulated pathway.
Journal Dev Cell
Abstract Autophagy is an essential degradative pathway in neurons, yet little is known about mechanisms driving autophagy in highly polarized cells. Here, we use dual-color live-cell imaging to investigate the neuron-specific mechanisms of constitutive autophagosome biogenesis in primary dorsal root ganglion (DRG) and hippocampal cultures. Under basal conditions, autophagosomes are continuously generated in the axon tip. There is an ordered assembly of proteins recruited with stereotypical kinetics onto the developing autophagosome. Plasma- or mitochondrial-derived membranes were not incorporated into nascent autophagosomes in the distal axon. Rather, autophagosomes are generated at double FYVE-containing protein 1 (DFCP1)-positive subdomains of the endoplasmic reticulum (ER), distinct from ER exit sites. Biogenesis events are enriched distally; autophagosomes form infrequently in dendrites, the soma, or midaxon, consistent with a compartmentalized pathway for constitutive autophagy in primary neurons. Distal biogenesis may facilitate degradation of damaged mitochondria and long-lived cytoplasmic proteins reaching the axon tip via slow axonal transport.
Volume 30(1)
Pages 71-85
Published 2014-7-14
DOI 10.1016/j.devcel.2014.06.001
PII S1534-5807(14)00345-1
PMID 25026034
PMC PMC4109719
MeSH Animals Autophagy* Axons / metabolism Biological Transport Cell Membrane / metabolism Cells, Cultured Dendritic Cells / cytology Dendritic Cells / metabolism Endoplasmic Reticulum / metabolism* Hippocampus / cytology Hippocampus / metabolism* Membrane Proteins / metabolism* Mice Mice, Transgenic Mitochondria / metabolism Neurons / cytology Neurons / metabolism* Phagosomes / physiology*
IF 10.092
Times Cited 143
Mice RBRC00806