TY - JOUR
T1 - Expanded genetic screening in caenorhabditis elegans identifies new regulators and an inhibitory role for NAD + in axon regeneration
AU - Kim, Kyung Won
AU - Tang, Ngang Heok
AU - Piggott, Christopher A.
AU - Andrusiak, Matthew G.
AU - Park, Seungmee
AU - Zhu, Ming
AU - Kurup, Naina
AU - Cherra, Salvatore J.
AU - Wu, Zilu
AU - Chisholm, Andrew D.
AU - Jin, Yishi
N1 - Publisher Copyright:
© Kim et al.
PY - 2018/11/1
Y1 - 2018/11/1
N2 - 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.
AB - 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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U2 - 10.7554/eLife.39756
DO - 10.7554/eLife.39756
M3 - Article
C2 - 30461420
AN - SCOPUS:85058600314
SN - 2050-084X
VL - 7
JO - eLife
JF - eLife
M1 - e39756
ER -