RRC ID 59365
Author Kim KW, Tang NH, Piggott CA, Andrusiak MG, Park S, Zhu M, Kurup N, Cherra SJ 3rd, Wu Z, Chisholm AD, Jin Y.
Title Expanded genetic screening in Caenorhabditis elegans identifies new regulators and an inhibitory role for NAD+ in axon regeneration.
Journal Elife
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.
Volume 7
Published 2018-11-21
DOI 10.7554/eLife.39756
PII 39756
PMID 30461420
PMC PMC6281318
MeSH Actin Cytoskeleton / metabolism Actin Cytoskeleton / ultrastructure Animals Axons / metabolism* Axons / ultrastructure Axotomy Caenorhabditis elegans / genetics* Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism Extracellular Matrix / chemistry Extracellular Matrix / metabolism Gene Expression Profiling Gene Expression Regulation Gene Ontology Genetic Testing Kelch Repeat Membrane Transport Proteins / genetics Membrane Transport Proteins / metabolism Microtubules / metabolism Microtubules / ultrastructure Molecular Sequence Annotation NAD / metabolism* Nerve Regeneration / genetics* Nicotinamide-Nucleotide Adenylyltransferase / genetics* Nicotinamide-Nucleotide Adenylyltransferase / metabolism
IF 7.551
Times Cited 7
C.elegans tm2905 tm6342 tm3502 tm6438 tm4762 tm4796 tm1087 tm1567 tm3116 tm1954