Drought events have become more severe under climate change,and this can pose a major threat to the survival of various organisms.The molecular mechanisms involved in dehydration resistance are not well known.Here,adu...Drought events have become more severe under climate change,and this can pose a major threat to the survival of various organisms.The molecular mechanisms involved in dehydration resistance are not well known.Here,adults of the migratory locust,Locusta migratoria,were subjected to food-mediated dehydration,and adipokinetic hormone(AKH)signaling was found to play a key role in regulating dehydration resistance.Specifically,dehydration shortened the lifespan,increased the body weight loss,and reduced the water loss rate in adult locusts.Global transcriptome profiles revealed variations in tissue-specific gene expression between dehydration-resistant locusts and normal locusts.Importantly,dehydration selection and exposure induced prominent expression of AKH genes in the retrocerebral complex of adult locusts.Furthermore,individual knockdown of AKH1,AKH2,or AKH receptor(AKHR)accelerated water loss and shortened the lifespan of adult locusts under dehydration conditions,and trehalose supplementation ameliorated the negative effects caused by interference with AKH or AKHR.These findings demonstrated that AKH/AKHR signaling-dependent trehalose metabolism plays a crucial role in regulating locust dehydration resistance and thus provide novel insights into the regulatory mechanism underlying drought resistance.展开更多
Anautogenous mosquitoes must blood feed on a vertebrate host to produce eggs.Each gonadotrophic cycle is subdivided into a sugar-feeding previtellogenic phase that produces primary follicles and a blood meal-activated...Anautogenous mosquitoes must blood feed on a vertebrate host to produce eggs.Each gonadotrophic cycle is subdivided into a sugar-feeding previtellogenic phase that produces primary follicles and a blood meal-activated vitellogenic phase in which large numbers of eggs synchronously mature and are laid.Multiple endocrine factors including juvenile hormone(JH),insulin-like peptides(ILPs),ovary ecdysteroidogenic hormone(OEH),and 20-hydroxyecdysone(20E)coordinate each gonadotrophic cycle.Egg formation also requires nutrients from feeding that are stored in the fat body.Regulation of egg formation is best understood in Aedes aegypti but the role different endocrine factors play in regulating nutrient mobilization and storage remains unclear.In this study,we report that adult female Ae.aegypti maintained triacylglycerol(TAG)stores during the previtellogenic phase of the first gonadotrophic cycle while glycogen stores declined.In contrast,TAG and glycogen stores were rapidly mobilized during the vitellogenic phase and then replenishment.Several genes encoding enzymes with functions in TAG and glycogen metabolism were differentially expressed in the fat body,which suggested regulation was mediated in part at the transcriptional level.Gain of function assays indicated that stored nutrients were primarily mobilized by adipokinetic hormone(AKH)while juvenoids and OEH regulated replenishment.ILP3 further showed evidence of negatively regulating certain lipolytic enzymes.Loss of function assays indicated AKH depends on the AKH receptor(AKHR)for function.Altogether,our results indicate that the opposing activities of different hormones regulate nutrient stores during a gonadotrophic cycle in Ae.aegypti.展开更多
The C2-α-mannosyl-tryptophan amino acid is produced by a unique posttranslational modification(PTM)of proteins and poses a significant synthetic challenge.A new strategy based on Pd-catalyzed auxiliary-directed remot...The C2-α-mannosyl-tryptophan amino acid is produced by a unique posttranslational modification(PTM)of proteins and poses a significant synthetic challenge.A new strategy based on Pd-catalyzed auxiliary-directed remote C-H glycosylation of tryptophan was developed,which generates the C2-α-mannopyranose(Man)-Trp unit in a highly efficient and stereoselective fashion.Density functional theory(DFT)computational studies support a concerted oxidative addition mechanism for the stereospecific functionalization of a Pd(II)palladacycle intermediate with anα-mannosyl chloride donor.The utility of this method was demonstrated in the first total synthesis of insect C-glycopeptide hormone Cam-HrTH-I.展开更多
mobilization of body fat is essential for energy homeostasis in animals. In insects, the adipokinetic hormone (Akh) systemically controls body fat mobilization. Biochemical evidence supports that Akh signals via a G...mobilization of body fat is essential for energy homeostasis in animals. In insects, the adipokinetic hormone (Akh) systemically controls body fat mobilization. Biochemical evidence supports that Akh signals via a G protein-coupled receptor (GPCR) called Akh receptor (AkhR) using cyclic-AMP (cAMP) and Ca2+ second messengers to induce storage lipid release from fat body cells. Recently, we provided genetic evidence that the intracellular calcium (iCa2+) level in fat storage cells controls adiposity in the fruit fly Drosophila melanogaster. However, little is known about the genes, which mediate Akh signalling downstream of the AkhR to regulate changes in iCa2+. Here, we used thermogenetics to provide in vivo evidence that the GPCR signal transducers G protein α q subunit (Gαq), G protein γ1 (Gγ1) and Phospholipase C at 21C (Plc21C) control cellular and organismal fat storage in Drosophila. Transgenic modulation of Gαq, Gγ1 and Plc21C affected the iCa2+ of fat body cells and the expression profile of the lipid metabolism effector genes midway and brummer, which results in severely obese or lean flies. Moreover, functional impairment of Gαq, Gγ1 and Plc21C antagonised Akh-induced fat depletion. This study characterizes Gαq, Gγ1 and Plc21C as anti-obesity genes and supports the model that Akh employs the Gαq/Gγ1/Plc21C module of iCa2+ control to regulate lipid mobilization in adult Drosophila.展开更多
基金supported by the National Key Research and Development Program of China(2022YFD1400503)the National Natural Science Foundation of China(32102208)the Hebei Natural Science Foundation,China(C2022201042,C2021201052 and C2023201075).
文摘Drought events have become more severe under climate change,and this can pose a major threat to the survival of various organisms.The molecular mechanisms involved in dehydration resistance are not well known.Here,adults of the migratory locust,Locusta migratoria,were subjected to food-mediated dehydration,and adipokinetic hormone(AKH)signaling was found to play a key role in regulating dehydration resistance.Specifically,dehydration shortened the lifespan,increased the body weight loss,and reduced the water loss rate in adult locusts.Global transcriptome profiles revealed variations in tissue-specific gene expression between dehydration-resistant locusts and normal locusts.Importantly,dehydration selection and exposure induced prominent expression of AKH genes in the retrocerebral complex of adult locusts.Furthermore,individual knockdown of AKH1,AKH2,or AKH receptor(AKHR)accelerated water loss and shortened the lifespan of adult locusts under dehydration conditions,and trehalose supplementation ameliorated the negative effects caused by interference with AKH or AKHR.These findings demonstrated that AKH/AKHR signaling-dependent trehalose metabolism plays a crucial role in regulating locust dehydration resistance and thus provide novel insights into the regulatory mechanism underlying drought resistance.
基金provided by the National Institutes of Health(R01AI033108,R01AI106892)awarded to MRS and MRBNational Science Foundation(IOS 1656236)awarded to MRS and MRB+3 种基金United States Department of Agriculture Hatch Project GEO00772 to MRSthe Pulliam Endowment(MRS)partially supported by the National Natural Science Foundation(31901876)the Natural Science Foundation of Jiangsu Province(KB20190900).
文摘Anautogenous mosquitoes must blood feed on a vertebrate host to produce eggs.Each gonadotrophic cycle is subdivided into a sugar-feeding previtellogenic phase that produces primary follicles and a blood meal-activated vitellogenic phase in which large numbers of eggs synchronously mature and are laid.Multiple endocrine factors including juvenile hormone(JH),insulin-like peptides(ILPs),ovary ecdysteroidogenic hormone(OEH),and 20-hydroxyecdysone(20E)coordinate each gonadotrophic cycle.Egg formation also requires nutrients from feeding that are stored in the fat body.Regulation of egg formation is best understood in Aedes aegypti but the role different endocrine factors play in regulating nutrient mobilization and storage remains unclear.In this study,we report that adult female Ae.aegypti maintained triacylglycerol(TAG)stores during the previtellogenic phase of the first gonadotrophic cycle while glycogen stores declined.In contrast,TAG and glycogen stores were rapidly mobilized during the vitellogenic phase and then replenishment.Several genes encoding enzymes with functions in TAG and glycogen metabolism were differentially expressed in the fat body,which suggested regulation was mediated in part at the transcriptional level.Gain of function assays indicated that stored nutrients were primarily mobilized by adipokinetic hormone(AKH)while juvenoids and OEH regulated replenishment.ILP3 further showed evidence of negatively regulating certain lipolytic enzymes.Loss of function assays indicated AKH depends on the AKH receptor(AKHR)for function.Altogether,our results indicate that the opposing activities of different hormones regulate nutrient stores during a gonadotrophic cycle in Ae.aegypti.
基金The experimental studies of this work were funded by NSFC-91753124,NSFC-21672105,NSFC-21421062,and NSFC-21725204 grants.
文摘The C2-α-mannosyl-tryptophan amino acid is produced by a unique posttranslational modification(PTM)of proteins and poses a significant synthetic challenge.A new strategy based on Pd-catalyzed auxiliary-directed remote C-H glycosylation of tryptophan was developed,which generates the C2-α-mannopyranose(Man)-Trp unit in a highly efficient and stereoselective fashion.Density functional theory(DFT)computational studies support a concerted oxidative addition mechanism for the stereospecific functionalization of a Pd(II)palladacycle intermediate with anα-mannosyl chloride donor.The utility of this method was demonstrated in the first total synthesis of insect C-glycopeptide hormone Cam-HrTH-I.
基金supported by the Max Planck Society and by the German research foundation(No.DFG KU 2866/1-1 toR.P.K.)
文摘mobilization of body fat is essential for energy homeostasis in animals. In insects, the adipokinetic hormone (Akh) systemically controls body fat mobilization. Biochemical evidence supports that Akh signals via a G protein-coupled receptor (GPCR) called Akh receptor (AkhR) using cyclic-AMP (cAMP) and Ca2+ second messengers to induce storage lipid release from fat body cells. Recently, we provided genetic evidence that the intracellular calcium (iCa2+) level in fat storage cells controls adiposity in the fruit fly Drosophila melanogaster. However, little is known about the genes, which mediate Akh signalling downstream of the AkhR to regulate changes in iCa2+. Here, we used thermogenetics to provide in vivo evidence that the GPCR signal transducers G protein α q subunit (Gαq), G protein γ1 (Gγ1) and Phospholipase C at 21C (Plc21C) control cellular and organismal fat storage in Drosophila. Transgenic modulation of Gαq, Gγ1 and Plc21C affected the iCa2+ of fat body cells and the expression profile of the lipid metabolism effector genes midway and brummer, which results in severely obese or lean flies. Moreover, functional impairment of Gαq, Gγ1 and Plc21C antagonised Akh-induced fat depletion. This study characterizes Gαq, Gγ1 and Plc21C as anti-obesity genes and supports the model that Akh employs the Gαq/Gγ1/Plc21C module of iCa2+ control to regulate lipid mobilization in adult Drosophila.