Improving protein quality and grain yield traits coordinately is an important goal for crop breeding.To date,many protein-quality or grain-yield regulation genes have been identified.However,the genetic strategies int...Improving protein quality and grain yield traits coordinately is an important goal for crop breeding.To date,many protein-quality or grain-yield regulation genes have been identified.However,the genetic strategies integrating these genes in good-protein-quality and high-yield crop breeding practice are far from established.Here,we characterized the functions of the MADS domain-containing protein Zm MADS8 and Zea mays G protein gamma subunit 1(Zm GG1)in regulating protein quality and grain yield of maize.Zm MADS8 positively regulates zein protein accumulation and negatively regulates nonzein protein and lysine levels in kernels by interacting with Zm MADS47 to promote the transcriptional activation of Opaque2.Additionally,Zm MADS8 regulates starch content of kernels by targeting genes involved in starch biosynthesis.Zm GG1,a putative interactor of Zm MADS8,negatively regulates kernel number with a trade-off effect on kernel starch accumulation.The mads8;zmgg1 double mutant improved protein quality by attenuating zein biosynthesis and increasing essential lysine level,and increased grain yield by increasing kernel number,compensating for decreased starch biosynthesis.Our findings revealed the biological function of Zm MADS8 and Zm GG1 in regulating protein quality and yield related traits and suggested a genetic strategy by direct editing of Zm MADS8 and Zm GG1 to improve grain yield and protein quality simultaneously.展开更多
[Objective]The aim is to perform prokaryotic expression of the glycoprotein gene of infectious hnematopoietic necrosis virus and polyclonal antibody preparation. [Methods]Glycoprotein gene( G) of infectious hematopoie...[Objective]The aim is to perform prokaryotic expression of the glycoprotein gene of infectious hnematopoietic necrosis virus and polyclonal antibody preparation. [Methods]Glycoprotein gene( G) of infectious hematopoietic tissue( IHNV) was synthesized,cloned to prokaryotic expression system pET-30a vector,yielding the recombinant plasmid pET-30a-IHNV-G. The yielded pET-30a-IHNV-G was transformed into E. coli strain BL21( DE3) plySs. [Results] SDSPAGE and Western blot results showed that protein G successfully expressed in E. coli at 37 ℃,1 mmol /L IPTG induction for 4 h. The molecular weight of fusion G protein was 57 KD. The polyclonal antibody was prepared by immunizing mice with the product of gel purification. ELISA analysis showed that the serum titer reached 1∶10 000. [Conclusion]The expressed G protein and the serum with polyclonal antibody obtained in this study provided the theoretical basis for the development of IHNV vaccine and detection of colloidal gold test strip.展开更多
Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease.Adult hippocampal neurogenesis is reduced in patients with Alzheimer’s disease.Exercise stimulates adult hippocampal neurogenesis in rode...Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease.Adult hippocampal neurogenesis is reduced in patients with Alzheimer’s disease.Exercise stimulates adult hippocampal neurogenesis in rodents and improves memory and slows cognitive decline in patients with Alzheimer’s disease.However,the molecular pathways for exercise-induced adult hippocampal neurogenesis and improved cognition in Alzheimer’s disease are poorly understood.Recently,regulator of G protein signaling 6(RGS6)was identified as the mediator of voluntary running-induced adult hippocampal neurogenesis in mice.Here,we generated novel RGS6fl/fl;APP_(SWE) mice and used retroviral approaches to examine the impact of RGS6 deletion from dentate gyrus neuronal progenitor cells on voluntary running-induced adult hippocampal neurogenesis and cognition in an amyloid-based Alzheimer’s disease mouse model.We found that voluntary running in APP_(SWE) mice restored their hippocampal cognitive impairments to that of control mice.This cognitive rescue was abolished by RGS6 deletion in dentate gyrus neuronal progenitor cells,which also abolished running-mediated increases in adult hippocampal neurogenesis.Adult hippocampal neurogenesis was reduced in sedentary APP_(SWE) mice versus control mice,with basal adult hippocampal neurogenesis reduced by RGS6 deletion in dentate gyrus neural precursor cells.RGS6 was expressed in neurons within the dentate gyrus of patients with Alzheimer’s disease with significant loss of these RGS6-expressing neurons.Thus,RGS6 mediated voluntary running-induced rescue of impaired cognition and adult hippocampal neurogenesis in APP_(SWE) mice,identifying RGS6 in dentate gyrus neural precursor cells as a possible therapeutic target in Alzheimer’s disease.展开更多
BACKGROUND Regulator of G protein signaling(RGS)proteins participate in tumor formation and metastasis by acting on theα-subunit of heterotrimeric G proteins.The speci-fic effect of RGS,particularly RGS4,on the progr...BACKGROUND Regulator of G protein signaling(RGS)proteins participate in tumor formation and metastasis by acting on theα-subunit of heterotrimeric G proteins.The speci-fic effect of RGS,particularly RGS4,on the progression of gastric cancer(GC)is not yet clear.AIM To explore the role and underlying mechanisms of action of RGS4 in GC develop-ment.METHODS The prognostic significance of RGS4 in GC was analyzed using bioinformatics based public databases and verified by immunohistochemistry and quantitative polymerase chain reaction in 90 patients with GC.Function assays were employed to assess the carcinogenic impact of RGS4,and the mechanism of its possible influence was detected by western blot analysis.A nude mouse xenograft model was established to study the effects of RGS4 on GC growth in vitro.RESULTS RGS4 was highly expressed in GC tissues compared with matched adjacent normal tissues.Elevated RGS4 expression was correlated with increased tumor-node-metastasis stage,increased tumor grade as well as poorer overall survival in patients with GC.Cell experiments demonstrated that RGS4 knockdown suppressed GC cell proliferation,migration and invasion.Similarly,xenograft experiments confirmed that RGS4 silencing significantly inhibited tumor growth.Moreover,RGS4 knockdown resulted in reduced phosphorylation levels of focal adhesion kinase,phosphatidyl-inositol-3-kinase,and protein kinase B,decreased vimentin and N-cadherin,and elevated E-cadherin.CONCLUSION High RGS4 expression in GC indicates a worse prognosis and RGS4 is a prognostic marker.RGS4 influences tumor progression via the focal adhesion kinase/phosphatidyl-inositol-3-kinase/protein kinase B pathway and epithelial-mesenchymal transition.展开更多
Osteoarthritis(OA)is a prevalent degenerative joint disorder marked by chronic pain,inflammation,and cartilage loss,with current treatments limited to symptom relief.G protein-coupled receptors(GPCRs)play a pivotal ro...Osteoarthritis(OA)is a prevalent degenerative joint disorder marked by chronic pain,inflammation,and cartilage loss,with current treatments limited to symptom relief.G protein-coupled receptors(GPCRs)play a pivotal role in OA progression by regulating inflammation,chondrocyte survival,and matrix homeostasis.However,their multifaceted signaling,via G proteins orβ-arrestins,poses challenges for precise therapeutic targeting.Biased agonism,where ligands selectively activate specific GPCR pathways,emerges as a promising approach to optimize efficacy and reduce side effects.This review examines biased signaling in OAassociated GPCRs,including cannabinoid receptors(CB1,CB2),chemokine receptors(CCR2,CXCR4),protease-activated receptors(PAR-2),adenosine receptors(A1R,A2AR,A2BR,A3R),melanocortin receptors(MC1R,MC3R),bradykinin receptors(B2R),prostaglandin E2 receptors(EP-2,EP-4),and calcium-sensing receptors(CaSR).We analyze ligands in clinical trials and explore natural products from Traditional Chinese Medicine as potential biased agonists.These compounds,with diverse structures and bioactivities,offer novel therapeutic avenues.By harnessing biased agonism,this review underscores the potential for developing targeted,safer OA therapies that address its complex pathology,bridging molecular insights with clinical translation.展开更多
Heterotrimeric G protein serves as a central hub in plant signal transduction,playing a pivotal role in integrating endogenous developmental signals and external environmental cues.While significant advances have been...Heterotrimeric G protein serves as a central hub in plant signal transduction,playing a pivotal role in integrating endogenous developmental signals and external environmental cues.While significant advances have been made in understanding G protein signaling mechanisms in model plants such as Arabidopsis and major crops like rice and maize,the precise regulatory roles in growth,development,and adaptation in horticultural crops are still poorly understood.In this review,we systematically summarize recent advances in uncovering both conserved and species-specific regulatory mechanisms of G protein signaling across diverse plant species.We also highlight key discoveries on the crosstalk between G protein-mediated pathways and other signaling cascades,such as hormone signaling,transcriptional regulation,and stress response networks.Finally,we discuss the potential applications of G protein signaling research in future crop improvement,offering new perspectives for advancing sustainable horticultural production.展开更多
目的 探究血清多聚嘧啶区结合蛋白1(polypyrimidine tract binding protein 1,PTBP1)、G蛋白信号调节因子2(regulator of G protein signaling 2,RGS2)、5-羟色胺(5-hydroxytryptamine, 5-HT)水平在慢性萎缩性胃炎(chronic atrophic gas...目的 探究血清多聚嘧啶区结合蛋白1(polypyrimidine tract binding protein 1,PTBP1)、G蛋白信号调节因子2(regulator of G protein signaling 2,RGS2)、5-羟色胺(5-hydroxytryptamine, 5-HT)水平在慢性萎缩性胃炎(chronic atrophic gastritis, CAG)诊断及病情严重程度评估中的价值。方法 选取2022年1月至2024年10月我院收治的143例CAG患者为研究组,根据胃固有腺体减少程度分为轻度组(n=26)、中度组(n=75)、重度组(n=42)。另纳入152名体检健康人群为对照组。采用酶联免疫吸附法(enzyme linked immunosorbent assay, ELISA)测定各组血清PTBP1、RGS2、5-HT的表达。Logistic回归分析CAG影响因素。ROC曲线分析血清PTBP1、RGS2、5-HT对CAG的诊断及病情严重程度评估价值。结果 与对照组相比,研究组血清PTBP1、RGS2、5-HT表达均升高(P<0.05)。重度组血清PTBP1、RGS2、5-HT高于轻度组、中度组(P<0.05),中度组血清PTBP1、5-HT高于轻度组(P<0.05)。PTBP1、RGS2、5-HT均为CAG发生的危险因素(P<0.05)。血清PTBP1、RGS2、5-HT联合诊断CAG的AUC为0.957,显著大于PTBP1(Z=6.160,P<0.001)、RGS2(Z=4.240,P<0.001)、5-HT(Z=3.248,P=0.001)单独诊断的AUC。PTBP1、RGS2、5-HT联合诊断重度CAG的AUC为0.973,显著大于PTBP1(Z=3.799,P<0.001)、RGS2(Z=5.018,P<0.001)单独诊断的AUC,与5-HT(Z=1.760,P=0.078)单独诊断的AUC,差异无统计学意义。结论 CAG患者血清PTBP1、RGS2、5-HT水平均升高,三者联合具有一定的CAG诊断及病情严重程度评估价值。展开更多
综述了G蛋白偶联受体(G protein coupled receptor,GPCR)二聚化检测的生物化学、生物物理、结构生物学方法,系统阐述了相关原理与关键要点,并对比分析了优势与局限性。未来研究应聚焦于开发更加灵敏且非侵入性的GPCR二聚化检测方法,推...综述了G蛋白偶联受体(G protein coupled receptor,GPCR)二聚化检测的生物化学、生物物理、结构生物学方法,系统阐述了相关原理与关键要点,并对比分析了优势与局限性。未来研究应聚焦于开发更加灵敏且非侵入性的GPCR二聚化检测方法,推动多种技术手段的协同联用,从而深入探索GPCR二聚体在疾病发生和发展中的作用,为药物设计提供新思路,并进一步发掘其在作物病虫害防治与畜牧业的应用潜力。展开更多
GNAO1-associated disorder is a rare disease and an example of developmental and epileptic encephalopathies.Caused by ca.150 different dominant missense mutations in the gene encoding the major neuronal G protein Gao,i...GNAO1-associated disorder is a rare disease and an example of developmental and epileptic encephalopathies.Caused by ca.150 different dominant missense mutations in the gene encoding the major neuronal G protein Gao,it spans a wide range of neurological clinical manifestations,that may include epileptic seizures,motor dysfunctions,developmental and intellectual delay,and other symptoms(Sáez González et al.,2023).展开更多
基金supported by the Biological Breeding-National Science and Technology Major Project(2023ZD0406804,2023ZD0402701)Major Project of Hubei Hongshan Laboratory(2022hszd019)First-Class Discipline Construction Funds of the College of Plant Science and Technology at Huazhong Agricultural University(2022ZK PY002)。
文摘Improving protein quality and grain yield traits coordinately is an important goal for crop breeding.To date,many protein-quality or grain-yield regulation genes have been identified.However,the genetic strategies integrating these genes in good-protein-quality and high-yield crop breeding practice are far from established.Here,we characterized the functions of the MADS domain-containing protein Zm MADS8 and Zea mays G protein gamma subunit 1(Zm GG1)in regulating protein quality and grain yield of maize.Zm MADS8 positively regulates zein protein accumulation and negatively regulates nonzein protein and lysine levels in kernels by interacting with Zm MADS47 to promote the transcriptional activation of Opaque2.Additionally,Zm MADS8 regulates starch content of kernels by targeting genes involved in starch biosynthesis.Zm GG1,a putative interactor of Zm MADS8,negatively regulates kernel number with a trade-off effect on kernel starch accumulation.The mads8;zmgg1 double mutant improved protein quality by attenuating zein biosynthesis and increasing essential lysine level,and increased grain yield by increasing kernel number,compensating for decreased starch biosynthesis.Our findings revealed the biological function of Zm MADS8 and Zm GG1 in regulating protein quality and yield related traits and suggested a genetic strategy by direct editing of Zm MADS8 and Zm GG1 to improve grain yield and protein quality simultaneously.
文摘[Objective]The aim is to perform prokaryotic expression of the glycoprotein gene of infectious hnematopoietic necrosis virus and polyclonal antibody preparation. [Methods]Glycoprotein gene( G) of infectious hematopoietic tissue( IHNV) was synthesized,cloned to prokaryotic expression system pET-30a vector,yielding the recombinant plasmid pET-30a-IHNV-G. The yielded pET-30a-IHNV-G was transformed into E. coli strain BL21( DE3) plySs. [Results] SDSPAGE and Western blot results showed that protein G successfully expressed in E. coli at 37 ℃,1 mmol /L IPTG induction for 4 h. The molecular weight of fusion G protein was 57 KD. The polyclonal antibody was prepared by immunizing mice with the product of gel purification. ELISA analysis showed that the serum titer reached 1∶10 000. [Conclusion]The expressed G protein and the serum with polyclonal antibody obtained in this study provided the theoretical basis for the development of IHNV vaccine and detection of colloidal gold test strip.
基金supported by the National Institutes of Health,Nos.AA025919,AA025919-03S1,and AA025919-05S1(all to RAF).
文摘Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease.Adult hippocampal neurogenesis is reduced in patients with Alzheimer’s disease.Exercise stimulates adult hippocampal neurogenesis in rodents and improves memory and slows cognitive decline in patients with Alzheimer’s disease.However,the molecular pathways for exercise-induced adult hippocampal neurogenesis and improved cognition in Alzheimer’s disease are poorly understood.Recently,regulator of G protein signaling 6(RGS6)was identified as the mediator of voluntary running-induced adult hippocampal neurogenesis in mice.Here,we generated novel RGS6fl/fl;APP_(SWE) mice and used retroviral approaches to examine the impact of RGS6 deletion from dentate gyrus neuronal progenitor cells on voluntary running-induced adult hippocampal neurogenesis and cognition in an amyloid-based Alzheimer’s disease mouse model.We found that voluntary running in APP_(SWE) mice restored their hippocampal cognitive impairments to that of control mice.This cognitive rescue was abolished by RGS6 deletion in dentate gyrus neuronal progenitor cells,which also abolished running-mediated increases in adult hippocampal neurogenesis.Adult hippocampal neurogenesis was reduced in sedentary APP_(SWE) mice versus control mice,with basal adult hippocampal neurogenesis reduced by RGS6 deletion in dentate gyrus neural precursor cells.RGS6 was expressed in neurons within the dentate gyrus of patients with Alzheimer’s disease with significant loss of these RGS6-expressing neurons.Thus,RGS6 mediated voluntary running-induced rescue of impaired cognition and adult hippocampal neurogenesis in APP_(SWE) mice,identifying RGS6 in dentate gyrus neural precursor cells as a possible therapeutic target in Alzheimer’s disease.
基金Supported by the Fundamental Research Program of Shanxi Province,No.202203021222418Research Program of Shanxi Provincial Health Commission,No.2023061+2 种基金Fundamental Research Cooperation Program of Beijing-Tianjin-Hebei Region of Natural Science Foundation of Tianjin,No.22JCZXJC00140Tianjin Major Science and Technology Project,No.21ZXJBSY00110Tianjin Health and Science and Technology Project,No.TJWJ2024ZK001.
文摘BACKGROUND Regulator of G protein signaling(RGS)proteins participate in tumor formation and metastasis by acting on theα-subunit of heterotrimeric G proteins.The speci-fic effect of RGS,particularly RGS4,on the progression of gastric cancer(GC)is not yet clear.AIM To explore the role and underlying mechanisms of action of RGS4 in GC develop-ment.METHODS The prognostic significance of RGS4 in GC was analyzed using bioinformatics based public databases and verified by immunohistochemistry and quantitative polymerase chain reaction in 90 patients with GC.Function assays were employed to assess the carcinogenic impact of RGS4,and the mechanism of its possible influence was detected by western blot analysis.A nude mouse xenograft model was established to study the effects of RGS4 on GC growth in vitro.RESULTS RGS4 was highly expressed in GC tissues compared with matched adjacent normal tissues.Elevated RGS4 expression was correlated with increased tumor-node-metastasis stage,increased tumor grade as well as poorer overall survival in patients with GC.Cell experiments demonstrated that RGS4 knockdown suppressed GC cell proliferation,migration and invasion.Similarly,xenograft experiments confirmed that RGS4 silencing significantly inhibited tumor growth.Moreover,RGS4 knockdown resulted in reduced phosphorylation levels of focal adhesion kinase,phosphatidyl-inositol-3-kinase,and protein kinase B,decreased vimentin and N-cadherin,and elevated E-cadherin.CONCLUSION High RGS4 expression in GC indicates a worse prognosis and RGS4 is a prognostic marker.RGS4 influences tumor progression via the focal adhesion kinase/phosphatidyl-inositol-3-kinase/protein kinase B pathway and epithelial-mesenchymal transition.
基金supported by the National Key R&D Program of the Ministry of Science and Technology(2023YFC2509900)National Natural Science Foundation of China(82374106)+3 种基金National Natural Science Foundation of China(U22A20371)the Basic and Applied Basic Research Fund of Guangdong Province(2021B1515120061)the Shenzhen Science and Technology Innovation Committee(JCYJ20210324102006017)SZ-HK Joint Laboratory for Innovative Biomaterials under CAS-HK Joint Laboratories(2024-2028).
文摘Osteoarthritis(OA)is a prevalent degenerative joint disorder marked by chronic pain,inflammation,and cartilage loss,with current treatments limited to symptom relief.G protein-coupled receptors(GPCRs)play a pivotal role in OA progression by regulating inflammation,chondrocyte survival,and matrix homeostasis.However,their multifaceted signaling,via G proteins orβ-arrestins,poses challenges for precise therapeutic targeting.Biased agonism,where ligands selectively activate specific GPCR pathways,emerges as a promising approach to optimize efficacy and reduce side effects.This review examines biased signaling in OAassociated GPCRs,including cannabinoid receptors(CB1,CB2),chemokine receptors(CCR2,CXCR4),protease-activated receptors(PAR-2),adenosine receptors(A1R,A2AR,A2BR,A3R),melanocortin receptors(MC1R,MC3R),bradykinin receptors(B2R),prostaglandin E2 receptors(EP-2,EP-4),and calcium-sensing receptors(CaSR).We analyze ligands in clinical trials and explore natural products from Traditional Chinese Medicine as potential biased agonists.These compounds,with diverse structures and bioactivities,offer novel therapeutic avenues.By harnessing biased agonism,this review underscores the potential for developing targeted,safer OA therapies that address its complex pathology,bridging molecular insights with clinical translation.
基金supported by the National Natural Science Foundation of China(Grant Nos.32172650,32430092)the Starry Night Science Fund of Zhejiang University Shanghai Institute for Advanced Study(Grant No.SN-ZJU-SIAS-0011)+1 种基金the Fundamental Research Funds for the Central Universities of China(Grant No.226-2024-00119)the Innovative Development of Horticulture Discipline of Zhejiang University(Grant No.B231220.0005-25).
文摘Heterotrimeric G protein serves as a central hub in plant signal transduction,playing a pivotal role in integrating endogenous developmental signals and external environmental cues.While significant advances have been made in understanding G protein signaling mechanisms in model plants such as Arabidopsis and major crops like rice and maize,the precise regulatory roles in growth,development,and adaptation in horticultural crops are still poorly understood.In this review,we systematically summarize recent advances in uncovering both conserved and species-specific regulatory mechanisms of G protein signaling across diverse plant species.We also highlight key discoveries on the crosstalk between G protein-mediated pathways and other signaling cascades,such as hormone signaling,transcriptional regulation,and stress response networks.Finally,we discuss the potential applications of G protein signaling research in future crop improvement,offering new perspectives for advancing sustainable horticultural production.
文摘综述了G蛋白偶联受体(G protein coupled receptor,GPCR)二聚化检测的生物化学、生物物理、结构生物学方法,系统阐述了相关原理与关键要点,并对比分析了优势与局限性。未来研究应聚焦于开发更加灵敏且非侵入性的GPCR二聚化检测方法,推动多种技术手段的协同联用,从而深入探索GPCR二聚体在疾病发生和发展中的作用,为药物设计提供新思路,并进一步发掘其在作物病虫害防治与畜牧业的应用潜力。
文摘GNAO1-associated disorder is a rare disease and an example of developmental and epileptic encephalopathies.Caused by ca.150 different dominant missense mutations in the gene encoding the major neuronal G protein Gao,it spans a wide range of neurological clinical manifestations,that may include epileptic seizures,motor dysfunctions,developmental and intellectual delay,and other symptoms(Sáez González et al.,2023).
