المؤلفون: Rosalind Hussey, Supriya Srinivasan, Ying K. Zhang, Tiffany T. Locke, Jaleh Mesgarzadeh, Jon Stieglitz, Frank C. Schroeder

المصدر: PLoS Genetics
Hussey, R, Stieglitz, J, Mesgarzadeh, J, Locke, T T, Zhang, Y K, Schroeder, F C & Srinivasan, S 2017, ' Pheromone-sensing neurons regulate peripheral lipid metabolism in Caenorhabditis elegans ', PLoS Genetics, vol. 13, no. 5, e1006806 . https://doi.org/10.1371/journal.pgen.1006806Test
PLoS Genetics, Vol 13, Iss 5, p e1006806 (2017)

مصطلحات موضوعية: 0301 basic medicine, Cancer Research, Nematoda, Regulator, Adipose tissue, GTP-Binding Protein alpha Subunits, Gi-Go, Biochemistry, Second Messenger Systems, Pheromones, Fats, Animal Cells, Medicine and Health Sciences, Cyclic AMP, Cyclic AMP/metabolism, Intestinal Mucosa, Pheromones/metabolism, Genetics (clinical), Caenorhabditis elegans, Neurons, Sensory Receptor Cells/metabolism, education.field_of_study, biology, Genetically Modified Organisms, Animal Models, Lipids, Cell biology, Adipose Tissue, Experimental Organism Systems, Second messenger system, Acetylcholine/metabolism, Anatomy, Cellular Types, Genetic Engineering, Acetylcholine, medicine.drug, Research Article, Biotechnology, lcsh:QH426-470, Sensory Receptor Cells, Population, Research and Analysis Methods, Caenorhabditis elegans Proteins/genetics, 03 medical and health sciences, Model Organisms, Genetics, medicine, Animals, education, Caenorhabditis elegans Proteins, Molecular Biology, GTP-Binding Protein alpha Subunits, Gi-Go/genetics, Ecology, Evolution, Behavior and Systematics, Genetically Modified Animals, Organisms, Biology and Life Sciences, Lipid metabolism, Cell Biology, biology.organism_classification, Lipid Metabolism, Invertebrates, Gastrointestinal Tract, lcsh:Genetics, 030104 developmental biology, Biological Tissue, Cellular Neuroscience, Caenorhabditis, Digestive System, Oils, Caenorhabditis elegans/genetics, Intestinal Mucosa/metabolism, Genetic screen, Neuroscience

الوصف: It is now established that the central nervous system plays an important role in regulating whole body metabolism and energy balance. However, the extent to which sensory systems relay environmental information to modulate metabolic events in peripheral tissues has remained poorly understood. In addition, it has been challenging to map the molecular mechanisms underlying discrete sensory modalities with respect to their role in lipid metabolism. In previous work our lab has identified instructive roles for serotonin signaling as a surrogate for food availability, as well as oxygen sensing, in the control of whole body metabolism. In this study, we now identify a role for a pair of pheromone-sensing neurons in regulating fat metabolism in C. elegans, which has emerged as a tractable and highly informative model to study the neurobiology of metabolism. A genetic screen revealed that GPA-3, a member of the Gα family of G proteins, regulates body fat content in the intestine, the major metabolic organ for C. elegans. Genetic and reconstitution studies revealed that the potent body fat phenotype of gpa-3 null mutants is controlled from a pair of neurons called ADL(L/R). We show that cAMP functions as the second messenger in the ADL neurons, and regulates body fat stores via the neurotransmitter acetylcholine, from downstream neurons. We find that the pheromone ascr#3, which is detected by the ADL neurons, regulates body fat stores in a GPA-3-dependent manner. We define here a third sensory modality, pheromone sensing, as a major regulator of body fat metabolism. The pheromone ascr#3 is an indicator of population density, thus we hypothesize that pheromone sensing provides a salient 'denominator' to evaluate the amount of food available within a population and to accordingly adjust metabolic rate and body fat levels.
Author summary The central nervous system plays a vital role in regulating whole body metabolism and energy balance. However, the precise cellular, genetic and molecular mechanisms underlying these effects remain a major unsolved mystery. C. elegans has emerged as a tractable and highly informative model to study the neurobiology of metabolism. Previously, we have identified instructive roles for serotonin signaling as a surrogate for food availability, as well as oxygen sensing, in the control of whole body metabolism. In our current study we have identified a role for a pair of pheromone-sensing neurons in regulating fat metabolism in C. elegans. cAMP acts as a second messenger in these neurons, and regulates body fat stores via acetylcholine signaling in the nervous system. We find that the population-density-sensing pheromone detected by these neurons regulates body fat stores. Together, we define a third sensory modality, population density sensing, as a major regulator of body fat metabolism.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b30e4478e3938cd045e9fcbd810a88ceTest
http://europepmc.org/articles/PMC5456406Test

المؤلفون: Peter E. A. Teal, Omer Durak, Fatma Kaplan, Arthur S. Edison, Paul W. Sternberg, Hans T. Alborn, Jagan Srinivasan, Rathika Nimalendran, Frank C. Schroeder, Parag Mahanti, Ramadan Ajredini

المصدر: PLoS ONE
PLoS ONE, Vol 6, Iss 3, p e17804 (2011)

مصطلحات موضوعية: Male, Cell signaling, lcsh:Medicine, Pheromones, Analytical Chemistry, 03 medical and health sciences, Behavioral Ecology, 0302 clinical medicine, Glycolipid, Gene expression, Chemical Biology, Animals, Mating, lcsh:Science, Caenorhabditis elegans, Biology, 030304 developmental biology, 0303 health sciences, Life Cycle Stages, Multidisciplinary, Chemical Ecology, biology, Ecology, fungi, lcsh:R, biology.organism_classification, Cell biology, Diet, Chemistry, Nematode, Sex pheromone, Larva, Pheromone, lcsh:Q, Glycolipids, 030217 neurology & neurosurgery, Research Article

الوصف: Background: The ascarosides form a family of small molecules that have been isolated from cultures of the nematode Caenorhabditis elegans. They are often referred to as “dauer pheromones” because most of them induce formation of long-lived and highly stress resistant dauer larvae. More recent studies have shown that ascarosides serve additional functions as social signals and mating pheromones. Thus, ascarosides have multiple functions. Until now, it has been generally assumed that ascarosides are constitutively expressed during nematode development. Methodology/Principal Findings: Cultures of C. elegans were developmentally synchronized on controlled diets. Ascarosides released into the media, as well as stored internally, were quantified by LC/MS. We found that ascaroside biosynthesis and release were strongly dependent on developmental stage and diet. The male attracting pheromone was verified to be a blend of at least four ascarosides, and peak production of the two most potent mating pheromone components, ascr#3 and asc#8 immediately preceded or coincided with the temporal window for mating. The concentration of ascr#2 increased under starvation conditions and peaked during dauer formation, strongly supporting ascr#2 as the main population density signal (dauer pheromone). After dauer formation, ascaroside production largely ceased and dauer larvae did not release any ascarosides. These findings show that both total ascaroside production and the relative proportions of individual ascarosides strongly correlate with these compounds' stage-specific biological functions. Conclusions/Significance: Ascaroside expression changes with development and environmental conditions. This is consistent with multiple functions of these signaling molecules. Knowledge of such differential regulation will make it possible to associate ascaroside production to gene expression profiles (transcript, protein or enzyme activity) and help to determine genetic pathways that control ascaroside biosynthesis. In conjunction with findings from previous studies, our results show that the pheromone system of C. elegans mimics that of insects in many ways, suggesting that pheromone signaling in C. elegans may exhibit functional homology also at the sensory level. In addition, our results provide a strong foundation for future behavioral modeling studies.

وصف الملف: application/pdf; application/postscript

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::64ad108d3b05984e275a38946f02633aTest
http://europepmc.org/articles/PMC3058051Test