Format

Send to

Choose Destination
Cell. 2016 Feb 25;164(5):1031-45. doi: 10.1016/j.cell.2016.01.032. Epub 2016 Feb 18.

Axon Degeneration Gated by Retrograde Activation of Somatic Pro-apoptotic Signaling.

Author information

1
Laboratory of Brain Development and Repair, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
2
Proteomics Resource Center, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
3
Laboratory of Brain Development and Repair, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA. Electronic address: marctl@rockefeller.edu.

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.

PMID:
26898330
PMCID:
PMC4785881
[Available on 2017-02-25]
DOI:
10.1016/j.cell.2016.01.032
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center