The Neuropeptide Receptor FRPR-8 Regulates Lifespan in a C. elegans Thermosensory Circuit
| Autor: | Yi-Han Lee, 李意涵 |
|---|---|
| Rok vydání: | 2019 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 107 Longevity is regulated by sensory experience, but the neural basis is incompletely understood. Previous studies have identified genes, neurons, and signals that maintain C. elegans lifespan at warmer temperature. Our previous work finds that the AFD thermosensory neuron secretes FLP-6, an FMRFamide neuropeptide essential for lifespan at warm temperature. Through screening C. elegans G protein-coupled receptors against a library of synthetic neuropeptides, we find that FRPR-8 is a likely candidate FLP-6 receptor. Lifespan reduction at warm temperature is observed in three frpr-8 alleles, phenocopying the flp-6 mutant. The flp-6; frpr-8 double mutant showed a lifespan similar to that of the frpr-8 mutant, suggesting that flp-6 and frpr-8 function in the same genetic pathway. Furthermore, frpr-8 mutations blocked the lifespan extension conferred by flp-6 overexpression, suggesting that frpr-8 acts downstream of flp-6. frpr-8 is expressed in the intestine as well as a few neurons, including the AWC and ASK chemosensory neurons, and the SIA and PVR interneurons. Although we failed to detect frpr-8 expression in AIY interneuron, expression of frpr-8 in the AIY interneuron, but not in the intestine or the ASK sensory neuron, fully rescued the short lifespan of the frpr-8 mutant. Consistent with our previous finding that flp-6 regulates longevity through daf-16/FoxO, our double mutant analysis suggests that frpr-8 and daf-16 act in a common longevity pathway. Progress in this project will improve our understanding of the circuit basis for longevity response to warm temperature in C. elegans. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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