title: Axonal autophagosomes use the ride-on service for retrograde transport toward the soma.
abstract: Degradation of autophagic vacuoles (AVs) via lysosomes is an important homeostatic process in cells. Neurons are highly polarized cells with long axons, thus facing special challenges to transport AVs generated at distal processes toward the soma where mature acidic lysosomes are relatively enriched. We recently revealed a new motor-adaptor sharing mechanism driving autophagosome transport to the soma. Late endosome (LE)-loaded dynein-SNAPIN motor-adaptor complexes mediate the retrograde transport of autophagosomes upon their fusion with LEs in distal axons. This motor-adaptor sharing mechanism enables neurons to maintain effective autophagic clearance in the soma, thus reducing autophagic stress in axons. Therefore, our study reveals a new cellular mechanism underlying the removal of distal AVs engulfing aggregated misfolded proteins and dysfunctional organelles associated with several major neurodegenerative diseases.
authors.affiliation: a Synaptic Function Section; National Institute of Neurological Disorders and Stroke; National Institutes of Health ; Bethesda , MD USA.
authors.forename: Xiu-Tang
authors.initials: XT
authors.lastname: Cheng
authors.forename: Bing
authors.initials: B
authors.lastname: Zhou
authors.forename: Mei-Yao
authors.initials: MY
authors.lastname: Lin
authors.forename: Qian
authors.initials: Q
authors.lastname: Cai
authors.forename: Zu-Hang
authors.initials: ZH
authors.lastname: Sheng
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D001369:Axons / Q000378:metabolism*; D001692:Biological Transport; D004398:Dyneins / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D010588:Phagosomes / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000378:metabolism
chemical_list: C118519:SNAPIN protein, human; D033921:Vesicular Transport Proteins; D004398:Dyneins
keywords: SNAPIN; amphisome; autophagic clearance; autophagosome; autophagy; axon; dynein; late endosome; lysosome; retrograde transport; syntaxin 17