TY - JOUR
T1 - The Apoptotic Engulfment Machinery Regulates Axonal Degeneration in C. elegans Neurons
AU - Nichols, Annika L.A.
AU - Meelkop, Ellen
AU - Linton, Casey
AU - Giordano-Santini, Rosina
AU - Sullivan, Robert K.
AU - Donato, Alessandra
AU - Nolan, Cara
AU - Hall, David H.
AU - Xue, Ding
AU - Neumann, Brent
AU - Hilliard, Massimo A.
N1 - Funding Information:
We thank Robert Parton, Rick Webb, and Robyn Webb for their invaluable help with electron microscopy and Fiona Ritchie for technical assistance. We thank Rowan Tweedale for comments on the manuscript, members of M.A.H.’s lab for discussions and comments, Michael Coleman and Erik Jorgensen for sharing reagents, and Erik Jorgensen and Randi Rawson for sharing unpublished results. Some strains were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440), and the International C. elegans Gene Knockout Consortium. This work was supported by NHMRC Project Grants 1067461 and 1068871, NIH R01 NS060129, and ARC Future Fellowship FT110100097 to M.A.H.; an NIH OD 010943 to David H. Hall; a University of Queensland Postdoctoral Fellowship to E.M.; The University of Queensland Research Scholarship to C.L.; a HFSP Long-Term Fellowship LT000762/2012 to R.G.-S.; a University of Queensland, International Postgraduate Award to A.D.; and an ARC LIEF grant LE130100078 for microscopy.
Publisher Copyright:
© 2016 The Authors.
PY - 2016/2/23
Y1 - 2016/2/23
N2 - Axonal degeneration is a characteristic feature of neurodegenerative disease and nerve injury. Here, we characterize axonal degeneration in Caenorhabditis elegans neurons following laser-induced axotomy. We show that this process proceeds independently of the WLDS and Nmnat pathway and requires the axonal clearance machinery that includes the conserved transmembrane receptor CED-1/Draper, the adaptor protein CED-6, the guanine nucleotide exchange factor complex Crk/Mbc/dCed-12 (CED-2/CED-5/CED-12), and the small GTPase Rac1 (CED-10). We demonstrate that CED-1 and CED-6 function non-cell autonomously in the surrounding hypodermis, which we show acts as the engulfing tissue for the severed axon. Moreover, we establish a function in this process for CED-7, an ATP-binding cassette (ABC) transporter, and NRF-5, a lipid-binding protein, both associated with release of lipid-vesicles during apoptotic cell clearance. Thus, our results reveal the existence of a WLDS/Nmnat-independent axonal degeneration pathway, conservation of the axonal clearance machinery, and a function for CED-7 and NRF-5 in this process.
AB - Axonal degeneration is a characteristic feature of neurodegenerative disease and nerve injury. Here, we characterize axonal degeneration in Caenorhabditis elegans neurons following laser-induced axotomy. We show that this process proceeds independently of the WLDS and Nmnat pathway and requires the axonal clearance machinery that includes the conserved transmembrane receptor CED-1/Draper, the adaptor protein CED-6, the guanine nucleotide exchange factor complex Crk/Mbc/dCed-12 (CED-2/CED-5/CED-12), and the small GTPase Rac1 (CED-10). We demonstrate that CED-1 and CED-6 function non-cell autonomously in the surrounding hypodermis, which we show acts as the engulfing tissue for the severed axon. Moreover, we establish a function in this process for CED-7, an ATP-binding cassette (ABC) transporter, and NRF-5, a lipid-binding protein, both associated with release of lipid-vesicles during apoptotic cell clearance. Thus, our results reveal the existence of a WLDS/Nmnat-independent axonal degeneration pathway, conservation of the axonal clearance machinery, and a function for CED-7 and NRF-5 in this process.
UR - http://www.scopus.com/inward/record.url?scp=84959155412&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84959155412&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2016.01.050
DO - 10.1016/j.celrep.2016.01.050
M3 - Article
C2 - 26876181
AN - SCOPUS:84959155412
SN - 2211-1247
VL - 14
SP - 1673
EP - 1683
JO - Cell Reports
JF - Cell Reports
IS - 7
ER -