DAF-16/FOXO promotes taste avoidance learning independently of axonal insulin-like signaling
| Autor: | Yuichi Iino, Takashi Nagashima, Masahiro Tomioka |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Cancer Research
Nematoda Physiology Social Sciences Sodium Chloride QH426-470 Biochemistry Learning and Memory Endocrinology 0302 clinical medicine Animal Cells Behavioral Conditioning Medicine and Health Sciences Psychology Insulin Protein Isoforms Post-Translational Modification Axon Genetics (clinical) Neurons 0303 health sciences Behavior Animal biology Chemotaxis Eukaryota Forkhead Transcription Factors Animal Models Cell biology Cell Motility medicine.anatomical_structure Experimental Organism Systems Caenorhabditis Elegans Taste Sensory Perception Cellular Types Signal transduction Signal Peptides Research Article Signal Transduction chemical and pharmacologic phenomena Research and Analysis Methods 03 medical and health sciences Model Organisms Avoidance Learning medicine Genetics Learning Animals Caenorhabditis elegans Proteins Molecular Biology Transcription factor Ecology Evolution Behavior and Systematics 030304 developmental biology Cell Nucleus Behavior Endocrine Physiology Insulin Signaling fungi Cognitive Psychology Organisms Biology and Life Sciences Proteins Epistasis Genetic Cell Biology Invertebrates Receptor Insulin Sensory neuron Insulin receptor Neuropeptide processing Cellular Neuroscience Mutation Animal Studies Caenorhabditis biology.protein Cognitive Science Neuron 030217 neurology & neurosurgery Neuroscience |
| Zdroj: | PLoS Genetics, Vol 15, Iss 7, p e1008297 (2019) PLoS Genetics |
| ISSN: | 1553-7404 1553-7390 |
| Popis: | 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. Author summary Animals change behavior based on remembered experiences of hunger and appetite. Signaling by insulin and insulin-like peptides in the nervous system plays key roles in behavioral responses to hunger and satiety. In C. elegans, insulin-like signaling in the gustatory sensory neuron ASER regulates learned avoidance of salt concentrations experienced during fasting, which we call taste avoidance learning. DAF-2c, an isoform of the insulin receptor homolog, is localized to the axon of ASER and regulates taste avoidance learning. Here, we show that DAF-16, the forkhead transcription factor O (FOXO) homolog, translocates into the nucleus of ASER during fasting and promotes taste avoidance learning. DAF-16 is negatively regulated by insulin-like signaling independently of axonal DAF-2c signaling. This dual function of insulin-like signaling in the cell body and the axon ensures dynamic changes in behavioral responses after experience of hunger. By genetic analyses using constitutively nuclear-translocated DAF-16, we show that DAF-16 in ASER regulates taste avoidance learning via modulating neuropeptide signaling in the nervous system, which is reminiscent of the function of FOXO in the hypothalamus in the regulation of food-seeking behavior in mammals. |
| Databáze: | OpenAIRE |
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