G protein-coupled receptors(GPCRs)are the largest family of membrane proteins in eukaryotes,with nearly 800 genes coding for these proteins.They are involved in many physiological processes,such as light perception,ta...G protein-coupled receptors(GPCRs)are the largest family of membrane proteins in eukaryotes,with nearly 800 genes coding for these proteins.They are involved in many physiological processes,such as light perception,taste and smell,neurotransmitter,metabolism,endocrine and exocrine,cell growth and migration.Importantly,GPCRs and their ligands are the targets of approximately one third of all marketed drugs.GPCRs are traditionally known for their role in transmitting signals from the extracellular environment to the cell's interior via the plasma membrane.However,emerging evidence suggests that GPCRs are also localized on mitochondria,where they play critical roles in modulating mitochondrial functions.These mitochondrial GPCRs(mGPCRs)can influence processes such as mitochondrial respiration,apoptosis,and reactive oxygen species(ROS)production.By interacting with mitochondrial signaling pathways,mGPCRs contribute to the regulation of energy metabolism and cell survival.Their presence on mitochondria adds a new layer of complexity to the understanding of cellular signaling,highlighting the organelle's role as not just an energy powerhouse but also a crucial hub for signal transduction.This expanding understanding of mGPCR function on mitochondria opens new avenues for research,particularly in the context of diseases where mitochondrial dysfunction plays a key role.Abnormalities in the phase conductance pathway of GPCRs located on mitochondria are closely associated with the development of systemic diseases such as cardiovascular disease,diabetes,obesity and Alzheimer's disease.In this review,we examined the various types of GPCRs identified on mitochondrial membranes and analyzed the complex relationships between mGPCRs and the pathogenesis of various diseases.We aim to provide a clearer understanding of the emerging significance of mGPCRs in health and disease,and to underscore their potential as therapeutic targets in the treatment of these conditions.展开更多
Sugar and protein are the major macronutrients＇ sources, and their balanced intake is important for animal＇s health. It has been observed that animals are able to change food preference in an imbalanced nutritional ...Sugar and protein are the major macronutrients＇ sources, and their balanced intake is important for animal＇s health. It has been observed that animals are able to change food preference in an imbalanced nutritional condition to selectively consume nutrients that are deficient in the body （Dethier, 1976）. Early studies in both Drosophila and mouse have demonstrated that animals exhibit food rejection to imbalanced diets lacking essential amino acids （Hao et al., 2005; Bjordal et al., 2014）. Furthermore, the food preference change upon protein depri- vation has been characterized using a two choice assay in Drosophila （Ribeiro and Dickson, 2010; Vargas et al., 2010）. Different from protein food, sugar is the main energy source, and sugar deficiency severely affects animal survival （Lee et al., 2008）. However, whether animals adopt a strategy of fast food preference switch upon sugar deprivation had not been investigated, and the neural mechanisms underlying this behavior regulation remain poorly understood.展开更多
Description Cellular membranes present natural borders for signal transduction between cells and their environment. Nature developed different strategies to enable signals to cross the membrane barrier. The goal of th...Description Cellular membranes present natural borders for signal transduction between cells and their environment. Nature developed different strategies to enable signals to cross the membrane barrier. The goal of this meeting is to discuss the molecular mechanisms of transmembrane signaling on the basis of three protein classes, i.e.展开更多
The superfamily of G protein-coupled receptors (GPCRs) contains immense structural and functional diversity and mediates a myriad of biological processes upon activation by various extracellular signals.Critical roles...The superfamily of G protein-coupled receptors (GPCRs) contains immense structural and functional diversity and mediates a myriad of biological processes upon activation by various extracellular signals.Critical roles of GPCRs have been established in bone development,remodeling,and disease.Multiple human GPCR mutations impair bone development or metabolism,resulting in osteopathologies.Here we summarize the disease phenotypes and dysfunctions caused by GPCR gene mutations in humans as well as by deletion in animals.To date,92 receptors (5 glutamate family,67 rhodopsin family,5 adhesion,4 frizzled/taste2 family,5 secretin family,and 6 other 7TM receptors) have been associated with bone diseases and dysfunctions (36 in humans and 72 in animals).By analyzing data from these 92 GPCRs,we found that mutation or deletion of different individual GPCRs could induce similar bone diseases or dysfunctions,and the same individual GPCR mutation or deletion could induce different bone diseases or dysfunctions in different populations or animal models.Data from human diseases or dysfunctions identified 19 genes whose mutation was associated with human BMD:9 genes each for human height and osteoporosis;4 genes each for human osteoarthritis (OA) and fracture risk;and 2 genes each for adolescent idiopathic scoliosis (AIS),periodontitis,osteosarcoma growth,and tooth development.Reports from gene knockout animals found 40 GPCRs whose deficiency reduced bone mass,while deficiency of 22 GPCRs increased bone mass and BMD;deficiency of 8 GPCRs reduced body length,while 5 mice had reduced femur size upon GPCR deletion.Furthermore,deficiency in 6 GPCRs induced osteoporosis;4 induced osteoarthritis;3 delayed fracture healing;3 reduced arthritis severity;and reduced bone strength,increased bone strength,and increased cortical thickness were each observed in 2 GPCR-deficiency models.The ever-expanding number of GPCR mutation-associated diseases warrants accelerated molecular analysis,population studies,and investigation of phenotype correlation with SNPs to elucidate GPCR function in human diseases.展开更多
基金supported the Fund of Sichuan Provincial Department of Science and Technology(Grant No.:2024YFFK0393)the CAMS Innovation Fund for Medical Sciences(CIFMS,Grant No.:2019-I2M-5-004).
文摘G protein-coupled receptors(GPCRs)are the largest family of membrane proteins in eukaryotes,with nearly 800 genes coding for these proteins.They are involved in many physiological processes,such as light perception,taste and smell,neurotransmitter,metabolism,endocrine and exocrine,cell growth and migration.Importantly,GPCRs and their ligands are the targets of approximately one third of all marketed drugs.GPCRs are traditionally known for their role in transmitting signals from the extracellular environment to the cell's interior via the plasma membrane.However,emerging evidence suggests that GPCRs are also localized on mitochondria,where they play critical roles in modulating mitochondrial functions.These mitochondrial GPCRs(mGPCRs)can influence processes such as mitochondrial respiration,apoptosis,and reactive oxygen species(ROS)production.By interacting with mitochondrial signaling pathways,mGPCRs contribute to the regulation of energy metabolism and cell survival.Their presence on mitochondria adds a new layer of complexity to the understanding of cellular signaling,highlighting the organelle's role as not just an energy powerhouse but also a crucial hub for signal transduction.This expanding understanding of mGPCR function on mitochondria opens new avenues for research,particularly in the context of diseases where mitochondrial dysfunction plays a key role.Abnormalities in the phase conductance pathway of GPCRs located on mitochondria are closely associated with the development of systemic diseases such as cardiovascular disease,diabetes,obesity and Alzheimer's disease.In this review,we examined the various types of GPCRs identified on mitochondrial membranes and analyzed the complex relationships between mGPCRs and the pathogenesis of various diseases.We aim to provide a clearer understanding of the emerging significance of mGPCRs in health and disease,and to underscore their potential as therapeutic targets in the treatment of these conditions.
基金supported by the grants from the National Science Foundation of China(Nos. 91132709 and 31130027)
文摘Sugar and protein are the major macronutrients＇ sources, and their balanced intake is important for animal＇s health. It has been observed that animals are able to change food preference in an imbalanced nutritional condition to selectively consume nutrients that are deficient in the body （Dethier, 1976）. Early studies in both Drosophila and mouse have demonstrated that animals exhibit food rejection to imbalanced diets lacking essential amino acids （Hao et al., 2005; Bjordal et al., 2014）. Furthermore, the food preference change upon protein depri- vation has been characterized using a two choice assay in Drosophila （Ribeiro and Dickson, 2010; Vargas et al., 2010）. Different from protein food, sugar is the main energy source, and sugar deficiency severely affects animal survival （Lee et al., 2008）. However, whether animals adopt a strategy of fast food preference switch upon sugar deprivation had not been investigated, and the neural mechanisms underlying this behavior regulation remain poorly understood.
文摘Description Cellular membranes present natural borders for signal transduction between cells and their environment. Nature developed different strategies to enable signals to cross the membrane barrier. The goal of this meeting is to discuss the molecular mechanisms of transmembrane signaling on the basis of three protein classes, i.e.
基金supported by grants from the National Key Research and Development Program of China(2018YFC1105102 to J.L.,2016YFC0902102 to J.L.and J.X.)the National Natural Science Foundation of China(81722020,91749204,81472048 to J.L.,81330049 to M.L.,81330059 and 81572640 to J.X.)+2 种基金the Innovation Program of Shanghai Municipal Education Commission(14ZZ051 to J.L.,2017ZZ01017 to J.X.)the Science and Technology Commission of Shanghai Municipality(12ZR1447900 to J.L.,17JC1400903 and 17411950300 to J.X.)the Fundamental Research Funds for the Central Universities(to J.L.)
文摘The superfamily of G protein-coupled receptors (GPCRs) contains immense structural and functional diversity and mediates a myriad of biological processes upon activation by various extracellular signals.Critical roles of GPCRs have been established in bone development,remodeling,and disease.Multiple human GPCR mutations impair bone development or metabolism,resulting in osteopathologies.Here we summarize the disease phenotypes and dysfunctions caused by GPCR gene mutations in humans as well as by deletion in animals.To date,92 receptors (5 glutamate family,67 rhodopsin family,5 adhesion,4 frizzled/taste2 family,5 secretin family,and 6 other 7TM receptors) have been associated with bone diseases and dysfunctions (36 in humans and 72 in animals).By analyzing data from these 92 GPCRs,we found that mutation or deletion of different individual GPCRs could induce similar bone diseases or dysfunctions,and the same individual GPCR mutation or deletion could induce different bone diseases or dysfunctions in different populations or animal models.Data from human diseases or dysfunctions identified 19 genes whose mutation was associated with human BMD:9 genes each for human height and osteoporosis;4 genes each for human osteoarthritis (OA) and fracture risk;and 2 genes each for adolescent idiopathic scoliosis (AIS),periodontitis,osteosarcoma growth,and tooth development.Reports from gene knockout animals found 40 GPCRs whose deficiency reduced bone mass,while deficiency of 22 GPCRs increased bone mass and BMD;deficiency of 8 GPCRs reduced body length,while 5 mice had reduced femur size upon GPCR deletion.Furthermore,deficiency in 6 GPCRs induced osteoporosis;4 induced osteoarthritis;3 delayed fracture healing;3 reduced arthritis severity;and reduced bone strength,increased bone strength,and increased cortical thickness were each observed in 2 GPCR-deficiency models.The ever-expanding number of GPCR mutation-associated diseases warrants accelerated molecular analysis,population studies,and investigation of phenotype correlation with SNPs to elucidate GPCR function in human diseases.
