| Title: | Rictor/TORC2 mediates gut-to-brain signaling in the regulation of phenotypic plasticity in C. elegans |
| Author(s): | O'Donnell MP; Chao PH; Kammenga JE; Sengupta P; |
| Address: | "Department of Biology and National Center for Behavioral Genomics, Brandeis University, Waltham, MA, United States of America. Laboratory of Nematology, Wageningen University and Research, Wageningen, The Netherlands" |
| DOI: | 10.1371/journal.pgen.1007213 |
| ISSN/ISBN: | 1553-7404 (Electronic) 1553-7390 (Print) 1553-7390 (Linking) |
| Abstract: | "Animals integrate external cues with information about internal conditions such as metabolic state to execute the appropriate behavioral and developmental decisions. Information about food quality and quantity is assessed by the intestine and transmitted to modulate neuronal functions via mechanisms that are not fully understood. The conserved Target of Rapamycin complex 2 (TORC2) controls multiple processes in response to cellular stressors and growth factors. Here we show that TORC2 coordinates larval development and adult behaviors in response to environmental cues and feeding state in the bacterivorous nematode C. elegans. During development, pheromone, bacterial food, and temperature regulate expression of the daf-7 TGF-beta and daf-28 insulin-like peptide in sensory neurons to promote a binary decision between reproductive growth and entry into the alternate dauer larval stage. We find that TORC2 acts in the intestine to regulate neuronal expression of both daf-7 and daf-28, which together reflect bacterial-diet dependent feeding status, thus providing a mechanism for integration of food signals with external cues in the regulation of neuroendocrine gene expression. In the adult, TORC2 similarly acts in the intestine to modulate food-regulated foraging behaviors via a PDF-2/PDFR-1 neuropeptide signaling-dependent pathway. We also demonstrate that genetic variation affects food-dependent larval and adult phenotypes, and identify quantitative trait loci (QTL) associated with these traits. Together, these results suggest that TORC2 acts as a hub for communication of feeding state information from the gut to the brain, thereby contributing to modulation of neuronal function by internal state" |
| Keywords: | "Adaptation, Physiological/genetics Animals Animals, Genetically Modified Brain/cytology/*metabolism Caenorhabditis elegans/embryology/*genetics/metabolism Caenorhabditis elegans Proteins/*physiology Gene Expression Regulation, Developmental Intestinal Muc;" |
| Notes: | "MedlineO'Donnell, Michael P Chao, Pin-Hao Kammenga, Jan E Sengupta, Piali eng F32 DC013711/DC/NIDCD NIH HHS/ T32 NS007292/NS/NINDS NIH HHS/ F32 DC013711/NH/NIH HHS/ R35 GM122463/GM/NIGMS NIH HHS/ T32 NS007292/NH/NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. 2018/02/08 PLoS Genet. 2018 Feb 7; 14(2):e1007213. doi: 10.1371/journal.pgen.1007213. eCollection 2018 Feb" |
