Jan 9, 2015

EFF-1-mediated regenerative axonal fusion requires components of the apoptotic pathway

Nature
Brent NeumannMassimo A Hilliard

Abstract

Functional regeneration after nervous system injury requires transected axons to reconnect with their original target tissue. Axonal fusion, a spontaneous regenerative mechanism identified in several species, provides an efficient means of achieving target reconnection as a regrowing axon is able to contact and fuse with its own separated axon fragment, thereby re-establishing the original axonal tract. Here we report a molecular characterization of this process in Caenorhabditis elegans, revealing dynamic changes in the subcellular localization of the EFF-1 fusogen after axotomy, and establishing phosphatidylserine (PS) and the PS receptor (PSR-1) as critical components for axonal fusion. PSR-1 functions cell-autonomously in the regrowing neuron and, instead of acting in its canonical signalling pathway, acts in a parallel phagocytic pathway that includes the transthyretin protein TTR-52, as well as CED-7, NRF-5 and CED-6 (refs 9, 10, 11, 12). We show that TTR-52 binds to PS exposed on the injured axon, and can restore fusion several hours after injury. We propose that PS functions as a 'save-me' signal for the distal fragment, allowing conserved apoptotic cell clearance molecules to function in re-establishing axonal integrit...Continue Reading

  • References30
  • Citations50

Citations

Mentioned in this Paper

Establishment and Maintenance of Localization
Biochemical Pathway
JMJD6
Apoptosis, Intrinsic Pathway
Phosphatidylserines
Caenorhabditis elegans
Hormone Receptors, Cell Surface
Entire Nervous System
Neurons
Psr-1 protein, C elegans

Related Feeds

Amyloidogenesis-associated Polyneuropathy

Familial Amyloid Neuropathies (FAP) are a rare group of autosomal dominant diseases in which nerves are compromised due to protein aggregation or fibril formation of transthyretin, apolipoprotein A1, or gelsolin proteins, resulting in nervous system dysfunction. Here is the latest research.

Related Papers

Developmental Dynamics : an Official Publication of the American Association of Anatomists
Brent NeumannMassimo A Hilliard
Current Biology : CB
Kenji Kontani, Joel H Rothman
The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Anindya Ghosh-RoyAndrew D Chisholm
© 2020 Meta ULC. All rights reserved