Neuronally Enriched RUFY3 Is Required for Caspase-Mediated Axon Degeneration. Academic Article uri icon

Overview

abstract

  • Selective synaptic and axonal degeneration are critical aspects of both brain development and neurodegenerative disease. Inhibition of caspase signaling in neurons is a potential therapeutic strategy for neurodegenerative disease, but no neuron-specific modulators of caspase signaling have been described. Using a mass spectrometry approach, we discovered that RUFY3, a neuronally enriched protein, is essential for caspase-mediated degeneration of TRKA+ sensory axons in vitro and in vivo. Deletion of Rufy3 protects axons from degeneration, even in the presence of activated CASP3 that is competent to cleave endogenous substrates. Dephosphorylation of RUFY3 at residue S34 appears required for axon degeneration, providing a potential mechanism for neurons to locally control caspase-driven degeneration. Neuronally enriched RUFY3 thus provides an entry point for understanding non-apoptotic functions of CASP3 and a potential target to modulate caspase signaling specifically in neurons for neurodegenerative disease.

publication date

  • June 17, 2019

Research

keywords

  • Axons
  • Nerve Degeneration
  • Nerve Tissue Proteins

Identity

PubMed Central ID

  • PMC8024238

Scopus Document Identifier

  • 85071349383

Digital Object Identifier (DOI)

  • 10.1016/j.neuron.2019.05.030

PubMed ID

  • 31221560

Additional Document Info

volume

  • 103

issue

  • 3