Reference - Detail
| 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 |
| Resource | |
| C.elegans | tm805 tm3036 tm3117 |