Expanded genetic screening in <i>Caenorhabditis elegans</i> identifies new regulators and an inhibitory role for NAD<sup>+</sup> in axon regeneration.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30461420.
- Also identified by DOI 10.7554/eLife.39756 and PMC identifier 6281318.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 <i>C. elegans</i> mechanosensory neuron axotomy model. We identify an unexpected role of the nicotinamide adenine dinucleotide (NAD<sup>+</sup>) 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.
Medical subject headings
- Axons
- Caenorhabditis elegans
- Caenorhabditis elegans Proteins
- NAD
- Nerve Regeneration
- Nicotinamide-Nucleotide Adenylyltransferase