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

Neumann, Brent, Coakley, Sean, Giordano-Santini, Rosina, Linton, Casey, Lee, Eui Seung, Nakagawa, Akihisa, Xue, Ding and Hilliard, Massimo A. (2015) EFF-1-mediated regenerative axonal fusion requires components of the apoptotic pathway. Nature, 517 7533: 219-222. doi:10.1038/nature14102

Author Neumann, Brent
Coakley, Sean
Giordano-Santini, Rosina
Linton, Casey
Lee, Eui Seung
Nakagawa, Akihisa
Xue, Ding
Hilliard, Massimo A.
Title EFF-1-mediated regenerative axonal fusion requires components of the apoptotic pathway
Journal name Nature   Check publisher's open access policy
ISSN 0028-0836
Publication date 2015-01-08
Sub-type Article (original research)
DOI 10.1038/nature14102
Open Access Status
Volume 517
Issue 7533
Start page 219
End page 222
Total pages 4
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Collection year 2016
Language eng
Formatted 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. 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.
Keyword Regeneration and repair in the nervous system
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2016 Collection
Version Filter Type
Citation counts: Scopus Citation Count Cited 9 times in Scopus Article | Citations
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Created: Mon, 12 Jan 2015, 12:17:13 EST by Dr Brent Neumann on behalf of Queensland Brain Institute