title: The Apoptotic Engulfment Machinery Regulates Axonal Degeneration in C. elegans Neurons.
abstract: 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 WLD(S) 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 WLD(S)/Nmnat-independent axonal degeneration pathway, conservation of the axonal clearance machinery, and a function for CED-7 and NRF-5 in this process.
authors.affiliation: Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Annika L A
authors.initials: ALA
authors.lastname: Nichols
authors.affiliation: Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Ellen
authors.initials: E
authors.lastname: Meelkop
authors.affiliation: Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Casey
authors.initials: C
authors.lastname: Linton
authors.affiliation: Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Rosina
authors.initials: R
authors.lastname: Giordano-Santini
authors.affiliation: Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Sullivan
authors.affiliation: Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Donato
authors.affiliation: Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Cara
authors.initials: C
authors.lastname: Nolan
authors.affiliation: Center for C. elegans Anatomy, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Hall
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Ding
authors.initials: D
authors.lastname: Xue
authors.affiliation: Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia. Electronic address: brent.neumann@monash.edu.
authors.forename: Brent
authors.initials: B
authors.lastname: Neumann
authors.affiliation: Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia. Electronic address: m.hilliard@uq.edu.au.
authors.forename: Massimo A
authors.initials: MA
authors.lastname: Hilliard
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins; D019771:Axotomy; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D005786:Gene Expression Regulation; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009410:Nerve Degeneration / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D050737:Proto-Oncogene Proteins c-crk / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; D051017:Apoptosis Regulatory Proteins; C407268:CED-10 protein, C elegans; C438369:CED-12 protein, C elegans; C111579:CED-5 protein, C elegans; C112888:CED-6 protein, C elegans; C112887:CED-7 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; C576460:NRF-5 protein, C elegans; D010750:Phosphoproteins; D050737:Proto-Oncogene Proteins c-crk; C422043:ced-1 protein, C elegans; D020744:rac GTP-Binding Proteins