RRC ID 45815
Author Neumann B, Coakley S, Giordano-Santini R, Linton C, Lee ES, Nakagawa A, Xue D, Hilliard MA.
Title EFF-1-mediated regenerative axonal fusion requires components of the apoptotic pathway.
Journal Nature
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 integrity during regeneration of the nervous system.
Volume 517(7533)
Pages 219-22
Published 2015-1-8
DOI 10.1038/nature14102
PII nature14102
PMID 25567286
MeSH ATP-Binding Cassette Transporters / metabolism Animals Apoptosis / physiology* Apoptosis Regulatory Proteins Axons / metabolism* Axons / pathology Caenorhabditis elegans / cytology* Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Carrier Proteins / metabolism Growth Cones / metabolism Membrane Glycoproteins / metabolism* Mutation Nerve Regeneration / physiology* Phagocytes / metabolism Phagocytosis Phosphatidylserines / metabolism Phosphoproteins / metabolism Receptors, Cell Surface / metabolism Signal Transduction Spectrin / genetics Spectrin / metabolism
IF 42.779
Times Cited 59
C.elegans tm2078 tm469