Expanded genetic screening in C. elegans identifies new regulators and an inhibitory role for NAD+ in axon regeneration
- University of California, San Diego, United States
Abstract
The mechanisms underlying axon regeneration in mature neurons are relevant to the understanding of normal nervous system maintenance and for developing therapeutic strategies for injury. Here, we report novel pathways in axon regeneration, identified by extending our previous function-based screen using the C. elegans mechanosensory neuron axotomy model. We identify an unexpected role of the nicotinamide adenine dinucleotide (NAD+) synthesizing enzyme, NMAT-2/NMNAT, in axon regeneration. NMAT-2 inhibits axon regrowth via cell-autonomous and non-autonomous mechanisms. NMAT-2 enzymatic activity is required to repress regrowth. Further, we find differential requirements for proteins in membrane contact site, components and regulators of the extracellular matrix, membrane trafficking, microtubule and actin cytoskeleton, the conserved Kelch-domain protein IVNS-1, and the orphan transporter MFSD-6 in axon regrowth. Identification of these new pathways expands our understanding of the molecular basis of axonal injury response and regeneration.
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All data generated or analysed during this study are included in the manuscript and supporting files.
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Funding
American Heart Association (13POST14800057)
- Kyung Won Kim
Canadian Institutes of Health Research (MFE-146808)
- Matthew G Andrusiak
National Institutes of Health (NS057317)
- Yishi Jin
National Institutes of Health (NS093588)
- Yishi Jin
Hallym University Research Fund (HRF-201809-014)
- Kyung Won Kim
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2018, Kim et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Expanded genetic screening in C. elegans identifies new regulators and an inhibitory role for NAD+ in axon regeneration
eLife 7:e39756.
https://doi.org/10.7554/eLife.39756
