Engulfing cells promote neuronal regeneration and remove neuronal debris through distinct biochemical functions of CED-1
Abstract
Two important biological events happen coincidently soon after nerve injury in the peripheral nervous system in C. elegans: removal of axon debris and initiation of axon regeneration. But, it is not known how these two events are co-regulated. Mutants of ced-1, a homolog of Draper and MEGF10, display defects in both events. One model is that those events could be related. But our data suggest that they are actually separable. CED-1 functions in the muscle-type engulfing cells in both events and is enriched in muscle protrusions in close contact with axon debris and regenerating axons. Its two functions occur through distinct biochemical mechanisms; extracellular domain-mediated adhesion for regeneration and extracellular domain binding-induced intracellular domain signaling for debris removal. These studies identify CED-1 in engulfing cells as a receptor in debris removal but as an adhesion molecule in neuronal regeneration, and have important implications for understanding neural circuit repair after injury.
Additional Information
© The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Received 06 March 2018; Accepted 22 October 2018; Published 19 November 2018. Data availability: The authors declare that all data supporting the findings of this study are available within the paper and its supplementary information file. This work was funded by grants from the March of Dimes Foundation (C.C.), the Whitehall Foundation Research Award (C.C.), the National Science Foundation (IOS-1455758 to C.C.), the Japan Student Services Organization Fellowship (N.S.), and the National Institutes of Health (5R01GM111320 to C.C. and 5R01GM098026 to C.-F.C.). We are deeply indebted to Ben Barres for his feedbacks to this work. His generosity in sharing data and information will be forever missed. We also thank Hanna Fares for TagRFP(S158T)::RAB-5 and TagRFP(S158T)::RAB-7 constructs, the Caenorhabditis Genetics Center for strains, and the WormBase for readily accessible information. Author Contributions: H.C. conceived, designed, performed, analyzed experiments, and drafted the article. Y.Z. designed, performed, and analyzed experiments. N.S. designed, performed, and analyzed experiments. Y-.W.H. acquired data for Supplementary Figure 9a-c. C-.F.C. conceived experiments and drafted the article. Y-.C.W. conceived experiments, contributed unpublished essential data and reagents, and drafted the article. C.C. conceived, designed, analyzed and interpreted data, and drafted the article. The authors declare no competing interests.Attached Files
Published - 41467_2018_Article_7291.pdf
Supplemental Material - 41467_2018_7291_MOESM1_ESM.pdf
Supplemental Material - 41467_2018_7291_MOESM2_ESM.pdf
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Additional details
- PMCID
- PMC6242819
- Eprint ID
- 91143
- Resolver ID
- CaltechAUTHORS:20181126-072928207
- March of Dimes Foundation
- Whitehall Foundation
- IOS-1455758
- NSF
- Japan Student Services Organization (JASSO)
- 5R01GM111320
- NIH
- 5R01GM098026
- NIH
- Created
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2018-11-26Created from EPrint's datestamp field
- Updated
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2021-11-16Created from EPrint's last_modified field