DAF-16/FOXO promotes taste avoidance learning independently of axonal insulin-like signaling

• Published in: PLoS genetics 2019-07, Vol.15 (7), p.e1008297-e1008297
• Main Authors: Nagashima, Takashi, Iino, Yuichi, Tomioka, Masahiro
• Format: Article
• Language: English
• Subjects: Animal behavior; Animals; Avoidance learning; Avoidance Learning - physiology; Axonal plasticity; Behavior, Animal; Behavioral plasticity; Biology and Life Sciences; Caenorhabditis elegans; Caenorhabditis elegans - physiology; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Cell body; Cell Nucleus - metabolism; Chemotaxis; Epistasis; Epistasis, Genetic; Food; Forkhead protein; Forkhead transcription factors; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - metabolism; Funding; Gene expression; Genetic aspects; Genetic engineering; Insulin; Insulin-like growth factors; Investigations; Isoforms; Kinases; Localization; Mass spectrometry; Medicine and Health Sciences; Memory; Metabolism; Mutation; Nematodes; Nervous system; Neurons; Nuclear transport; Peptides; Physiological aspects; Protein Isoforms - metabolism; Protein kinase C; Receptor, Insulin - genetics; Research and Analysis Methods; Salt; Scientific imaging; Signal Transduction; Signaling peptides and proteins; Social Sciences; Sodium Chloride - analysis; Starvation; Taste; Taste aversion; Taste aversion learning; Taste discrimination learning
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1008297

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.