RRC ID 53465
Author Nichols ALA, Meelkop E, Linton C, Giordano-Santini R, Sullivan RK, Donato A, Nolan C, Hall DH, Xue D, Neumann B, Hilliard MA.
Title The Apoptotic Engulfment Machinery Regulates Axonal Degeneration in C. elegans Neurons.
Journal Cell Rep
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.
Volume 14(7)
Pages 1673-1683
Published 2016-2-23
DOI 10.1016/j.celrep.2016.01.050
PII S2211-1247(16)30028-6
PMID 26876181
PMC PMC4821572
MeSH ATP-Binding Cassette Transporters / genetics* ATP-Binding Cassette Transporters / metabolism Animals Apoptosis / genetics* Apoptosis Regulatory Proteins Axotomy Caenorhabditis elegans / genetics* Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism Carrier Proteins / genetics* Carrier Proteins / metabolism Cytoskeletal Proteins / genetics Cytoskeletal Proteins / metabolism Epidermal Cells Epidermis / metabolism Gene Expression Regulation Membrane Proteins / genetics Membrane Proteins / metabolism Nerve Degeneration / genetics* Nerve Degeneration / metabolism Nerve Degeneration / pathology Neurons / metabolism* Neurons / pathology Phosphoproteins / genetics Phosphoproteins / metabolism Proto-Oncogene Proteins c-crk / genetics Proto-Oncogene Proteins c-crk / metabolism Signal Transduction rac GTP-Binding Proteins / genetics rac GTP-Binding Proteins / metabolism
IF 8.109
Times Cited 16
C.elegans tm805 tm3036 tm3117