Presentation/Session Information

Session Information

Session Title: Regeneration and Synaptic Function Session Type: Parallel
Session Location: De Neve Auditorium Session Time: Sat, Jun 27 8:30AM - 11:30AM

Presentation Information

Program Number: 165 Presentation Time: 8:42AM - 8:54AM

Presentation Content

EFF-1-mediated regenerative axonal fusion requires components of the apoptotic pathway.Brent Neumann 1,2, Sean Coakley 1, Rosina Giordano-Santini 1, Casey Linton 1, Eui Seung Lee 3, Akihisa Nakagawa 3, Ding Xue 3, Massimo A Hilliard 1. 1)Queensland Brain Institute, The University of Queensland, Brisbane QLD 4072, Australia; 2)Anatomy and Developmental Biology, Monash University, Clayton, Victoria 3800, Australia; 3)Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado 80309, USA

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.




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