The Apoptotic Engulfment Machinery Regulates Axonal Degeneration in C. elegans Neurons

Annika L A Nichols, Ellen Meelkop, Casey Linton, Rosina Giordano-Santini, Robert K. Sullivan, Alessandra Donato, Cara Nolan, David H. Hall, Ding Xue, Brent Neumann, Massimo A. Hilliard

Research output: Contribution to journalArticle

13 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)1673-1683
Number of pages11
JournalCell Reports
Volume14
Issue number7
DOIs
StatePublished - Feb 23 2016

Fingerprint

Neurons
Machinery
Lipids
Guanine Nucleotide Exchange Factors
Axotomy
ATP-Binding Cassette Transporters
Monomeric GTP-Binding Proteins
Subcutaneous Tissue
Caenorhabditis elegans
Neurodegenerative Diseases
Neurodegenerative diseases
Axons
Carrier Proteins
Lasers
Conservation
Wounds and Injuries
Cells
Tissue
Proteins

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Nichols, A. L. A., Meelkop, E., Linton, C., Giordano-Santini, R., Sullivan, R. K., Donato, A., ... Hilliard, M. A. (2016). The Apoptotic Engulfment Machinery Regulates Axonal Degeneration in C. elegans Neurons. Cell Reports, 14(7), 1673-1683. https://doi.org/10.1016/j.celrep.2016.01.050

The Apoptotic Engulfment Machinery Regulates Axonal Degeneration in C. elegans Neurons. / Nichols, Annika L A; Meelkop, Ellen; Linton, Casey; Giordano-Santini, Rosina; Sullivan, Robert K.; Donato, Alessandra; Nolan, Cara; Hall, David H.; Xue, Ding; Neumann, Brent; Hilliard, Massimo A.

In: Cell Reports, Vol. 14, No. 7, 23.02.2016, p. 1673-1683.

Research output: Contribution to journalArticle

Nichols, ALA, Meelkop, E, Linton, C, Giordano-Santini, R, Sullivan, RK, Donato, A, Nolan, C, Hall, DH, Xue, D, Neumann, B & Hilliard, MA 2016, 'The Apoptotic Engulfment Machinery Regulates Axonal Degeneration in C. elegans Neurons', Cell Reports, vol. 14, no. 7, pp. 1673-1683. https://doi.org/10.1016/j.celrep.2016.01.050
Nichols ALA, Meelkop E, Linton C, Giordano-Santini R, Sullivan RK, Donato A et al. The Apoptotic Engulfment Machinery Regulates Axonal Degeneration in C. elegans Neurons. Cell Reports. 2016 Feb 23;14(7):1673-1683. https://doi.org/10.1016/j.celrep.2016.01.050
Nichols, Annika L A ; Meelkop, Ellen ; Linton, Casey ; Giordano-Santini, Rosina ; Sullivan, Robert K. ; Donato, Alessandra ; Nolan, Cara ; Hall, David H. ; Xue, Ding ; Neumann, Brent ; Hilliard, Massimo A. / The Apoptotic Engulfment Machinery Regulates Axonal Degeneration in C. elegans Neurons. In: Cell Reports. 2016 ; Vol. 14, No. 7. pp. 1673-1683.
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