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

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14 Scopus citations

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

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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., Nolan, C., Hall, D. H., Xue, D., Neumann, B., & 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