Cell Reports
Volume 3, Issue 5, 30 May 2013, Pages 1422-1429
Journal home page for Cell Reports

Report
The Phr1 Ubiquitin Ligase Promotes Injury-Induced Axon Self-Destruction

https://doi.org/10.1016/j.celrep.2013.04.013Get rights and content
Under a Creative Commons license
open access

Highlights

  • Loss of the E3 ligase Phr1 strongly protects injured mammalian PNS and CNS axons

  • Phr1 functions within neurons to promote axon loss induced by diverse insults

  • Phr1 promotes axon degeneration by limiting the amount of the survival factor NMNAT2

Summary

Axon degeneration is an evolutionarily conserved process that drives the loss of damaged axons and is an early event in many neurological disorders, so it is important to identify the molecular constituents of this poorly understood mechanism. Here, we demonstrate that the Phr1 E3 ubiquitin ligase is a central component of this axon degeneration program. Loss of Phr1 results in prolonged survival of severed axons in both the peripheral and central nervous systems, as well as preservation of motor and sensory nerve terminals. Phr1 depletion increases the axonal level of the axon survival molecule nicotinamide mononucleotide adenyltransferase 2 (NMNAT2), and NMNAT2 is necessary for Phr1-dependent axon stability. The profound long-term protection of peripheral and central mammalian axons following Phr1 deletion suggests that pharmacological inhibition of Phr1 function may be an attractive therapeutic candidate for amelioration of axon loss in neurological disease.

Cited by (0)