The Apoptotic Engulfment Machinery Regulates Axonal Degeneration in C. elegans Neurons
| Autor: | Alessandra Donato, Massimo A. Hilliard, Ding Xue, Cara Nolan, Annika L.A. Nichols, Rosina Giordano-Santini, David H. Hall, Ellen Meelkop, Casey Linton, Brent Neumann, Robert K. P. Sullivan |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Apoptosis Biology Article General Biochemistry Genetics and Molecular Biology Apoptotic cell clearance 03 medical and health sciences Adapter molecule crk medicine Animals Small GTPase Axon Caenorhabditis elegans Caenorhabditis elegans Proteins Neurons fungi Membrane Proteins Signal transducing adaptor protein Axotomy Proto-Oncogene Proteins c-crk Phosphoproteins biology.organism_classification rac GTP-Binding Proteins Cell biology Rac GTP-Binding Proteins Cytoskeletal Proteins 030104 developmental biology medicine.anatomical_structure Epidermal Cells Gene Expression Regulation Nerve Degeneration ATP-Binding Cassette Transporters Guanine nucleotide exchange factor Epidermis Apoptosis Regulatory Proteins Carrier Proteins Signal Transduction |
| Zdroj: | Cell Reports. 14:1673-1683 |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2016.01.050 |
| Popis: | SummaryAxonal 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. |
| Databáze: | OpenAIRE |
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