RRC ID 59391
Author Noblett N, Wu Z, Ding ZH, Park S, Roenspies T, Flibotte S, Chisholm AD, Jin Y, Colavita A.
Title DIP-2 suppresses ectopic neurite sprouting and axonal regeneration in mature neurons.
Journal J Cell Biol
Abstract Neuronal morphology and circuitry established during early development must often be maintained over the entirety of animal lifespans. Compared with neuronal development, the mechanisms that maintain mature neuronal structures and architecture are little understood. The conserved disco-interacting protein 2 (DIP2) consists of a DMAP1-binding domain and two adenylate-forming domains (AFDs). We show that the Caenorhabditis elegans DIP-2 maintains morphology of mature neurons. dip-2 loss-of-function mutants display a progressive increase in ectopic neurite sprouting and branching during late larval and adult life. In adults, dip-2 also inhibits initial stages of axon regeneration cell autonomously and acts in parallel to DLK-1 MAP kinase and EFA-6 pathways. The function of DIP-2 in maintenance of neuron morphology and in axon regrowth requires its AFD domains and is independent of its DMAP1-binding domain. Our findings reveal a new conserved regulator of neuronal morphology maintenance and axon regrowth after injury.
Volume 218(1)
Pages 125-133
Published 2019-1-7
DOI 10.1083/jcb.201804207
PII jcb.201804207
PMID 30396999
PMC PMC6314549
MeSH Animals Caenorhabditis elegans / genetics* Caenorhabditis elegans / growth & development Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cytoskeletal Proteins / genetics Cytoskeletal Proteins / metabolism* Gene Expression Regulation, Developmental Larva / genetics* Larva / growth & development Larva / metabolism MAP Kinase Kinase Kinases / genetics MAP Kinase Kinase Kinases / metabolism Mutation Nerve Regeneration / genetics* Neuronal Outgrowth / genetics Neuronal Plasticity / genetics* Neurons / metabolism* Neurons / ultrastructure Nuclear Proteins / genetics* Nuclear Proteins / metabolism Protein Interaction Domains and Motifs Signal Transduction
IF 8.891
Times Cited 2
C.elegans tm745 tm3124 tm1422 tm2807