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.
journal_name
Celljournal_title
Cellauthors
Simon DJ,Pitts J,Hertz NT,Yang J,Yamagishi Y,Olsen O,Tešić Mark M,Molina H,Tessier-Lavigne Mdoi
10.1016/j.cell.2016.01.032subject
Has Abstractpub_date
2016-02-25 00:00:00pages
1031-45issue
5eissn
0092-8674issn
1097-4172pii
S0092-8674(16)30046-0journal_volume
164pub_type
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