title: Axon Degeneration Gated by Retrograde Activation of Somatic Pro-apoptotic Signaling.
abstract: During development, sensory axons compete for limiting neurotrophic support, and local neurotrophin insufficiency triggers caspase-dependent axon degeneration. The signaling driving axon degeneration upon local deprivation is proposed to reside within axons. Our results instead support a model in which, despite the apoptotic machinery being present in axons, the cell body is an active participant in gating axonal caspase activation and axon degeneration. Loss of trophic support in axons initiates retrograde activation of a somatic pro-apoptotic pathway, which, in turn, is required for distal axon degeneration via an anterograde pro-degenerative factor. At a molecular level, the cell body is the convergence point of two signaling pathways whose integrated action drives upregulation of pro-apoptotic Puma, which, unexpectedly, is confined to the cell body. Puma then overcomes inhibition by pro-survival Bcl-xL and Bcl-w and initiates the anterograde pro-degenerative program, highlighting the role of the cell body as an arbiter of large-scale axon removal.
authors.affiliation: Laboratory of Brain Development and Repair, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Simon
authors.affiliation: Laboratory of Brain Development and Repair, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Pitts
authors.affiliation: Laboratory of Brain Development and Repair, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Nicholas T
authors.initials: NT
authors.lastname: Hertz
authors.affiliation: Laboratory of Brain Development and Repair, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Laboratory of Brain Development and Repair, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Yamagishi
authors.affiliation: Laboratory of Brain Development and Repair, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Olav
authors.initials: O
authors.lastname: Olsen
authors.affiliation: Proteomics Resource Center, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Milica
authors.initials: M
authors.lastname: Tešić Mark
authors.affiliation: Proteomics Resource Center, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Henrik
authors.initials: H
authors.lastname: Molina
authors.affiliation: Laboratory of Brain Development and Repair, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA. Electronic address: marctl@rockefeller.edu.
authors.forename: Marc
authors.initials: M
authors.lastname: Tessier-Lavigne
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000737:chemistry / Q000378:metabolism; D001369:Axons / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008969:Molecular Sequence Data; D009410:Nerve Degeneration / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D011506:Proteins / Q000378:metabolism; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C494812:Bcl2l1 protein, mouse; C101155:Bcl2l2 protein, mouse; C488588:PUMA protein, mouse; D011506:Proteins; D025521:Tumor Suppressor Proteins; D051020:bcl-X Protein