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

作者：Simon, David J.; Pitts, Jason; Hertz, Nicholas T.; Yang, Jing; Yamagishi, Yuya; Olsen, Olav; Mark, Milica Tesic; Molina, Henrik; Tessier-Lavigne, Marc^*

来源：Cell, 2016, 164(5): 1031-1045.

DOI：10.1016/j.cell.2016.01.032

• CASPASE ACTIVITY
• NEURONAL APOPTOSIS
• PATHWAY
• DEATH
• DLK
• SUPPRESSES
• INHIBITOR
• INJURY
• PUMA

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 prodegenerative program, highlighting the role of the cell body as an arbiter of large-scale axon removal.

• 出版日期2016-2-25
• 单位北京大学