RRC ID 59562
著者 Nagashima T, Iino Y, Tomioka M.
タイトル DAF-16/FOXO promotes taste avoidance learning independently of axonal insulin-like signaling.
ジャーナル PLoS Genet
Abstract The avoidance of starvation is critical for the survival of most organisms, thus animals change behavior based on past nutritional conditions. Insulin signaling is important for nutritional state-dependent behavioral plasticity, yet the underlying regulatory mechanism at the cellular level remains unclear. Previous studies showed that insulin-like signaling is required for taste avoidance learning, in which the nematode Caenorhabditis elegans avoids salt concentrations encountered under starvation conditions. DAF-2c, a splice isoform of the DAF-2 insulin receptor, functions in the axon of the ASER sensory neuron, which senses changes in salt concentrations. In addition, mutants of a major downstream factor of DAF-2, the forkhead transcription factor O (FOXO) homolog DAF-16, show defects in taste avoidance learning. Interestingly, the defect of the daf-2 mutant is not suppressed by daf-16 mutations in the learning, unlike those in other phenomena, such as longevity and development. Here we show that multiple DAF-16 isoforms function in ASER. By epistasis analysis using a DAF-2c isoform-specific mutant and an activated form of DAF-16, we found that DAF-16 acts in the nucleus in parallel with the DAF-2c-dependent pathway in the axon, indicating that insulin-like signaling acts both in the cell body and axon of a single neuron, ASER. Starvation conditioning induces nuclear translocation of DAF-16 in ASER and degradation of DAF-16 before starvation conditioning causes defects in taste avoidance learning. Forced nuclear localization of DAF-16 in ASER biased chemotaxis towards lower salt concentrtions and this effect required the Gq/PKC pathway and neuropeptide processing enzymes. These data imply that DAF-16/FOXO transmits starvation signals and modulates neuropeptide transmission in the learning.
巻・号 15(7)
ページ e1008297
公開日 2019-7-1
DOI 10.1371/journal.pgen.1008297
PII PGENETICS-D-19-00023
PMID 31323047
PMC PMC6668909
MeSH Animals Avoidance Learning / physiology* Behavior, Animal Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism* Cell Nucleus / metabolism Epistasis, Genetic Forkhead Transcription Factors / genetics* Forkhead Transcription Factors / metabolism* Insulin Mutation Protein Isoforms / metabolism Receptor, Insulin / genetics Signal Transduction Sodium Chloride / analysis*
IF 5.224
引用数 1
リソース情報
線虫 tm5030 tm5031 tm6659 tm718