Although magnesium(Mg) is one of the most important nutrients, involved in many enzyme activities and the structural stabilization of tissues, its importance as a macronutrient ion has been overlooked in recent decade...Although magnesium(Mg) is one of the most important nutrients, involved in many enzyme activities and the structural stabilization of tissues, its importance as a macronutrient ion has been overlooked in recent decades by botanists and agriculturists, who did not regard Mg deficiency(MGD) in plants as a severe health problem. However, recent studies have shown,surprisingly, that Mg contents in historical cereal seeds have markedly declined over time, and two thirds of people surveyed in developed countries received less than their minimum daily Mg requirement. Thus, the mechanisms of response to MGD and ways to increase Mg contents in plants are two urgent practical problems. In this review, we discuss several aspects of MGD in plants, including phenotypic and physiological changes, cell Mg2+homeostasis control by Mg2+transporters, MGD signaling, interactions between Mg2+and other ions, and roles of Mg2+in plant secondary metabolism. Our aim is to improve understanding of the influence of MGD on plant growth and development and to advance crop breeding for Mg enrichment.展开更多
As a critical component of the tumor microenvironment(TME),cancerassociated fibroblasts(CAFs)play important roles in cancer initiation and progression.Well-known signaling pathways,including the transforming growth fa...As a critical component of the tumor microenvironment(TME),cancerassociated fibroblasts(CAFs)play important roles in cancer initiation and progression.Well-known signaling pathways,including the transforming growth factor-β(TGF-β),Hedgehog(Hh),Notch,Wnt,Hippo,nuclear factor kappa-B(NF-κB),Janus kinase(JAK)/signal transducer and activator of transcription(STAT),mitogen-activated protein kinase(MAPK),and phosphoinositide 3-kinase(PI3K)/AKT pathways,as well as transcription factors,including hypoxia-inducible factor(HIF),heat shock transcription factor 1(HSF1),P53,Snail,and Twist,constitute complex regulatory networks in theTMEtomodulate the formation,activation,heterogeneity,metabolic characteristics and malignant phenotype of CAFs.Activated CAFs remodel the TME and influence the malignant biological processes of cancer cells by altering the transcriptional and secretory characteristics,and this modulation partially depends on the regulation of signaling cascades.The results of preclinical and clinical trials indicated that therapies targeting signaling pathways in CAFs demonstrated promising efficacy but were also accompanied by some failures(e.g.,NCT01130142 and NCT01064622).Hence,a comprehensive understanding of the signaling cascades in CAFs might help us better understand the roles of CAFs and the TME in cancer progression and may facilitate the development of more efficient and safer stroma-targeted cancer therapies.Here,we review recent advances in studies of signaling pathways in CAFs and briefly discuss some future perspectives on CAF research.展开更多
Different from animals, sessile plants are equipped with a large receptor-like kinase(RLK) superfamily. RLKs are a family of single trans-membrane proteins with divergent N-terminal extracellular domains capped by a s...Different from animals, sessile plants are equipped with a large receptor-like kinase(RLK) superfamily. RLKs are a family of single trans-membrane proteins with divergent N-terminal extracellular domains capped by a signal peptide and C-terminal intracellular kinase. Researches in the last two decades have uncovered an increasing number of RLKs that regulate plant development, stress response and sexual reproduction, highlighting a dominant role of RLK signaling in cell-to-cell communications. Sexual reproduction in flowering plants is featured by interactions between the male gametophyte and the female tissues to facilitate sperm delivery and fertilization. Emerging evidences suggest that RLKs regulate almost every aspect of plant reproductive process, especially during pollination. Therefore, in this review we will focus mainly on the function and signaling of RLKs in plant male-female interaction and discuss the future prospects on these topics.展开更多
Arthropod-borne viruses cause serious threats to human health and global agriculture by rapidly spreading via insect vectors. Southern rice black-streaked dwarf virus (SRBSDV) is the most damaging rice-infecting virus...Arthropod-borne viruses cause serious threats to human health and global agriculture by rapidly spreading via insect vectors. Southern rice black-streaked dwarf virus (SRBSDV) is the most damaging rice-infecting virus that is frequently transmitted by planthoppers. However, the molecular mechanisms underlying its propagation in the host plants and epidemics in the field are largely unknown. Here, we showed that the SRBSDV-encoded P6 protein is a key effector that regulates rice ethylene signaling to coordinate viral infection and transmission. In early SRBSDV infection, P6 interacts with OsRTH2 in the cytoplasm to activate ethylene signaling and enhance SRBSDV proliferation;this also repels the insect vector to reduce infestation. In late infection, P6 enters the nucleus, where it interacts with OsEIL2, a key transcription factor of ethylene signaling. The P6-OsEIL2 interaction suppresses ethylene signaling by preventing the dimerization of OsEIL2, thereby facilitating viral transmission by attracting the insect vector. Collectively, these findings reveal a novel molecular mechanism by which an arbovirus modulates the host defense system to promote viral infection and transmission.展开更多
Lipid phosphorylation by diacylglycerol kinase(DGK)that produces phosphatidic acid(PA)plays important roles in various biological processes,including stress responses,but the underlying mechanisms remain elusive.Here,...Lipid phosphorylation by diacylglycerol kinase(DGK)that produces phosphatidic acid(PA)plays important roles in various biological processes,including stress responses,but the underlying mechanisms remain elusive.Here,we show that DGK5 and its lipid product PA suppress ABA biosynthesis by interacting withABA-DEFICIENT2(ABA2),a key ABA biosynthesis enzyme,to negatively modulate plant responseto abiotic stress tested in Arabidopsis thaliana.Loss of DGK5 function rendered plants less damaged,whereas overexpression(OE)of DGK5 enhanced plant damage to water and salt stress.The dgk5 mutant plants exhibited decreased total cellular and nuclear levels of PA with increased levels of diacylglycerol,whereas DGK5-OE plants displayed the opposite effect.Interestingly,we found that both DGK5 and PA bind to the ABA-synthesizing enzyme ABA2 and suppress its enzymatic activity.Consistently,the dgk5 mutant plants exhibited increased levels of ABA,while DGK5-OE plants showed reduced ABA levels.In addition,we showed that both DGK5 and ABA2 are detected in and outside the nuclei,and loss of DGK5 function decreased the nuclear association of ABA2.We found that both DGK5 activity and PA promote nuclear association of ABA2.Taken together,these results indicate that both DGK5 and PA interact with ABA2 to inhibit its enzymatic activity and promote its nuclear sequestration,thereby sup-pressing ABA production in response to abiotic stress.Our study reveals a sophisticated mechanism by which DGK5 and PA regulate plant stress responses.展开更多
Recently,a work jointly studied by Ling Li and coworkers1 was published in Nature Materials,describing a reconfigurable DNA origami nanodevice designed to regulate CD95 death-inducing signaling of immune cells.The res...Recently,a work jointly studied by Ling Li and coworkers1 was published in Nature Materials,describing a reconfigurable DNA origami nanodevice designed to regulate CD95 death-inducing signaling of immune cells.The researchers utilized the DNA origami nanodevice to establish selective local immune tolerance and demonstrated its ability to alleviate rheumatoid arthritis(RA)in the inflamed synovial tissue of mice without causing any obvious side effects(Fig.1).This approach presents a novel idea for the development of drug interventions involving ligandreceptor interactions.展开更多
β-Glucosidase has been reported to induce the production of herbivore-induced plant volatiles. How-ever, how it works remains unclear. Here, we investigated the levels of salicylic acid (SA), jasmonic acid (JA), ethy...β-Glucosidase has been reported to induce the production of herbivore-induced plant volatiles. How-ever, how it works remains unclear. Here, we investigated the levels of salicylic acid (SA), jasmonic acid (JA), ethylene, and H2O2, all of which are known signaling molecules that play important roles in in-duced plant defense in rice plants treated with β-glucosidase, and compared these to levels in plants infested by the rice brown planthopper Nilaparvata lugens (Stl). Results showed that wounding and treatment by β-glucosidase increased the levels of SA, ethylene, and H2O2, but not JA, in all plants compared to control plants. The signaling pathways activated by β-glucosidase treatment are similar to those activated by an infestation by N. lugens, although the magnitude and timing of the signals elicited by the two treatments are different. This may explain why both treatments have similar volatile profiles and are equally attractive to the parasitoid Anagrus nilaparvatae Pang et Wang.展开更多
能量平衡失调被认为是一个影响人类疾病的重要驱动因素,单磷酸腺苷活化的蛋白激酶(AMP-activated protein kinase,AMPK)作为一种重要的能量传感器,在维持能量稳态中的核心作用使其成为预防和治疗疾病的一个关键靶点。铁死亡作为一种新...能量平衡失调被认为是一个影响人类疾病的重要驱动因素,单磷酸腺苷活化的蛋白激酶(AMP-activated protein kinase,AMPK)作为一种重要的能量传感器,在维持能量稳态中的核心作用使其成为预防和治疗疾病的一个关键靶点。铁死亡作为一种新型细胞死亡方式,与多种疾病的病理生理过程有关,而AMPK相关信号通路又是调控铁死亡的重要途径,明确AMPK具体通过何种通路诱导或抑制铁死亡,将为未来疾病治疗提供新思路,为新药研究提供新靶点。该文通过整理国内外相关文献,挖掘了AMPK调控铁死亡的相关信号通路,并对AMPK调控铁死亡相关信号通路在疾病中的应用进行了综述,旨在为后期研究提供参考。展开更多
Receptor activity-modulating proteins(RAMPs)are accessory molecules that form complexes with specific G protein-coupled receptors(GPCRs)and modulate their functions.It is established that RAMP interacts with the gluca...Receptor activity-modulating proteins(RAMPs)are accessory molecules that form complexes with specific G protein-coupled receptors(GPCRs)and modulate their functions.It is established that RAMP interacts with the glucagon receptor family of GPCRs but the underlying mechanism is poorly understood.In this study,we used a bioluminescence resonance energy transfer(BRET)approach to comprehensively investigate such interactions.In conjunction with c AMP accumulation,Gaqactivation andβ-arrestin1/2 recruitment assays,we not only verified the GPCR-RAMP pairs previously reported,but also identified new patterns of GPCR-RAMP interaction.While RAMP1 was able to modify the three signaling events elicited by both glucagon receptor(GCGR)and glucagon-like peptide-1 receptor(GLP-1 R),and RAMP2 mainly affectedβ-arrestin1/2 recruitment by GCGR,GLP-1 R and glucagon-like peptide-2 receptor,RAMP3 showed a widespread negative impact on all the family members except for growth hormone-releasing hormone receptor covering the three pathways.Our results suggest that RAMP modulates both G protein dependent and independent signal transduction among the glucagon receptor family members in a receptor-specific manner.Mapping such interactions provides new insights into the role of RAMP in ligand recognition and receptor activation.展开更多
基金supported by the Science Foundation of Zhejiang Sci-Tech University(grant 14042008-Y)the Zhejiang Provincial Natural Science Foundation of China(grant number LY13C130001)+1 种基金the Zhejiang Provincial Top Key Discipline of Biology(grant number 2012A03-C)the National Natural Science Foundation of China(grant number 81373908)
文摘Although magnesium(Mg) is one of the most important nutrients, involved in many enzyme activities and the structural stabilization of tissues, its importance as a macronutrient ion has been overlooked in recent decades by botanists and agriculturists, who did not regard Mg deficiency(MGD) in plants as a severe health problem. However, recent studies have shown,surprisingly, that Mg contents in historical cereal seeds have markedly declined over time, and two thirds of people surveyed in developed countries received less than their minimum daily Mg requirement. Thus, the mechanisms of response to MGD and ways to increase Mg contents in plants are two urgent practical problems. In this review, we discuss several aspects of MGD in plants, including phenotypic and physiological changes, cell Mg2+homeostasis control by Mg2+transporters, MGD signaling, interactions between Mg2+and other ions, and roles of Mg2+in plant secondary metabolism. Our aim is to improve understanding of the influence of MGD on plant growth and development and to advance crop breeding for Mg enrichment.
基金National Natural Science Foundation of China,Grant/Award Numbers:81802352,82002541,81772555,81902428National Science Foundation for Distinguished Young Scholars of China,Grant/Award Number:81625016+4 种基金Shanghai Sailing Program,Grant/Award Number:20YF1409000Shanghai Rising-Star Program,Grant/Award Number:20QA1402100Shanghai Anticancer Association Young Eagle Program,Grant/Award Number:SACA-CY19A06Clinical and Scientific Innovation Project of Shanghai Hospital Development Center,Grant/Award Numbers:SHDC12018109,SHDC12019109Scientific Innovation Project of Shanghai Education Committee,Grant/Award Number:2019-01-07-00-07-E00057。
文摘As a critical component of the tumor microenvironment(TME),cancerassociated fibroblasts(CAFs)play important roles in cancer initiation and progression.Well-known signaling pathways,including the transforming growth factor-β(TGF-β),Hedgehog(Hh),Notch,Wnt,Hippo,nuclear factor kappa-B(NF-κB),Janus kinase(JAK)/signal transducer and activator of transcription(STAT),mitogen-activated protein kinase(MAPK),and phosphoinositide 3-kinase(PI3K)/AKT pathways,as well as transcription factors,including hypoxia-inducible factor(HIF),heat shock transcription factor 1(HSF1),P53,Snail,and Twist,constitute complex regulatory networks in theTMEtomodulate the formation,activation,heterogeneity,metabolic characteristics and malignant phenotype of CAFs.Activated CAFs remodel the TME and influence the malignant biological processes of cancer cells by altering the transcriptional and secretory characteristics,and this modulation partially depends on the regulation of signaling cascades.The results of preclinical and clinical trials indicated that therapies targeting signaling pathways in CAFs demonstrated promising efficacy but were also accompanied by some failures(e.g.,NCT01130142 and NCT01064622).Hence,a comprehensive understanding of the signaling cascades in CAFs might help us better understand the roles of CAFs and the TME in cancer progression and may facilitate the development of more efficient and safer stroma-targeted cancer therapies.Here,we review recent advances in studies of signaling pathways in CAFs and briefly discuss some future perspectives on CAF research.
基金supported by the Ministry of Science and Technology of China(2013CB945103)the National Natural Science Foundation of China(31330053)
文摘Different from animals, sessile plants are equipped with a large receptor-like kinase(RLK) superfamily. RLKs are a family of single trans-membrane proteins with divergent N-terminal extracellular domains capped by a signal peptide and C-terminal intracellular kinase. Researches in the last two decades have uncovered an increasing number of RLKs that regulate plant development, stress response and sexual reproduction, highlighting a dominant role of RLK signaling in cell-to-cell communications. Sexual reproduction in flowering plants is featured by interactions between the male gametophyte and the female tissues to facilitate sperm delivery and fertilization. Emerging evidences suggest that RLKs regulate almost every aspect of plant reproductive process, especially during pollination. Therefore, in this review we will focus mainly on the function and signaling of RLKs in plant male-female interaction and discuss the future prospects on these topics.
基金funded by the National Natural Science Foundation of China(31871928,31671993)the Guangdong Special Branch Plan for Young Talent with Scientific and Technological Innovation(2019TQ05N158)+2 种基金the Pearl River S&T Nova Program of Guangzhou(201906010093)the Research and Development Project in Major Fields of Guangdong(2019B020238001)the Guangdong Provincial Innovation Team for General Key Technologies in Modern Agricultural Industry(2019KJ133).
文摘Arthropod-borne viruses cause serious threats to human health and global agriculture by rapidly spreading via insect vectors. Southern rice black-streaked dwarf virus (SRBSDV) is the most damaging rice-infecting virus that is frequently transmitted by planthoppers. However, the molecular mechanisms underlying its propagation in the host plants and epidemics in the field are largely unknown. Here, we showed that the SRBSDV-encoded P6 protein is a key effector that regulates rice ethylene signaling to coordinate viral infection and transmission. In early SRBSDV infection, P6 interacts with OsRTH2 in the cytoplasm to activate ethylene signaling and enhance SRBSDV proliferation;this also repels the insect vector to reduce infestation. In late infection, P6 enters the nucleus, where it interacts with OsEIL2, a key transcription factor of ethylene signaling. The P6-OsEIL2 interaction suppresses ethylene signaling by preventing the dimerization of OsEIL2, thereby facilitating viral transmission by attracting the insect vector. Collectively, these findings reveal a novel molecular mechanism by which an arbovirus modulates the host defense system to promote viral infection and transmission.
基金Research reported in this article was supported by the National Institute of General Medical Sciences of the National Institutes of Health under award number R01GM141374 and the National Science Foundation grants 2222157 and 2302424.
文摘Lipid phosphorylation by diacylglycerol kinase(DGK)that produces phosphatidic acid(PA)plays important roles in various biological processes,including stress responses,but the underlying mechanisms remain elusive.Here,we show that DGK5 and its lipid product PA suppress ABA biosynthesis by interacting withABA-DEFICIENT2(ABA2),a key ABA biosynthesis enzyme,to negatively modulate plant responseto abiotic stress tested in Arabidopsis thaliana.Loss of DGK5 function rendered plants less damaged,whereas overexpression(OE)of DGK5 enhanced plant damage to water and salt stress.The dgk5 mutant plants exhibited decreased total cellular and nuclear levels of PA with increased levels of diacylglycerol,whereas DGK5-OE plants displayed the opposite effect.Interestingly,we found that both DGK5 and PA bind to the ABA-synthesizing enzyme ABA2 and suppress its enzymatic activity.Consistently,the dgk5 mutant plants exhibited increased levels of ABA,while DGK5-OE plants showed reduced ABA levels.In addition,we showed that both DGK5 and ABA2 are detected in and outside the nuclei,and loss of DGK5 function decreased the nuclear association of ABA2.We found that both DGK5 activity and PA promote nuclear association of ABA2.Taken together,these results indicate that both DGK5 and PA interact with ABA2 to inhibit its enzymatic activity and promote its nuclear sequestration,thereby sup-pressing ABA production in response to abiotic stress.Our study reveals a sophisticated mechanism by which DGK5 and PA regulate plant stress responses.
基金support from the National Natural Science Foundation of China(82072087,31970893,32270976)funding by Science and Technology Projects in Guangzhou(202206010087,China).
文摘Recently,a work jointly studied by Ling Li and coworkers1 was published in Nature Materials,describing a reconfigurable DNA origami nanodevice designed to regulate CD95 death-inducing signaling of immune cells.The researchers utilized the DNA origami nanodevice to establish selective local immune tolerance and demonstrated its ability to alleviate rheumatoid arthritis(RA)in the inflamed synovial tissue of mice without causing any obvious side effects(Fig.1).This approach presents a novel idea for the development of drug interventions involving ligandreceptor interactions.
基金the National Basic Research Program of China (Grant No. 2006CB102005)the National Natural Science Foundation of China (Grant No. 30270233)+2 种基金the Division of Science and Technology of Zhejiang Province (Grant No. 2006C30040)the Program for New Century Excellent Talents of the Ministry of Education of China (Grant No. NCET-04-0534)the Innovation Research Team Program of the Ministry of Education of China (Grant No. IRT0535)
文摘β-Glucosidase has been reported to induce the production of herbivore-induced plant volatiles. How-ever, how it works remains unclear. Here, we investigated the levels of salicylic acid (SA), jasmonic acid (JA), ethylene, and H2O2, all of which are known signaling molecules that play important roles in in-duced plant defense in rice plants treated with β-glucosidase, and compared these to levels in plants infested by the rice brown planthopper Nilaparvata lugens (Stl). Results showed that wounding and treatment by β-glucosidase increased the levels of SA, ethylene, and H2O2, but not JA, in all plants compared to control plants. The signaling pathways activated by β-glucosidase treatment are similar to those activated by an infestation by N. lugens, although the magnitude and timing of the signals elicited by the two treatments are different. This may explain why both treatments have similar volatile profiles and are equally attractive to the parasitoid Anagrus nilaparvatae Pang et Wang.
文摘能量平衡失调被认为是一个影响人类疾病的重要驱动因素,单磷酸腺苷活化的蛋白激酶(AMP-activated protein kinase,AMPK)作为一种重要的能量传感器,在维持能量稳态中的核心作用使其成为预防和治疗疾病的一个关键靶点。铁死亡作为一种新型细胞死亡方式,与多种疾病的病理生理过程有关,而AMPK相关信号通路又是调控铁死亡的重要途径,明确AMPK具体通过何种通路诱导或抑制铁死亡,将为未来疾病治疗提供新思路,为新药研究提供新靶点。该文通过整理国内外相关文献,挖掘了AMPK调控铁死亡的相关信号通路,并对AMPK调控铁死亡相关信号通路在疾病中的应用进行了综述,旨在为后期研究提供参考。
基金partially supported by the National Key R&D Programs of China(2018YFA0507000,Ming-Wei Wang)the National Science Foundation of China grants(81773792,Dehua Yang+4 种基金81973373 Dehua Yang81872915,Ming-Wei Wangand 82073904,Ming-Wei Wang)National Science and Technology Major Project of China-Key New Drug Creation and Manufacturing Program(2018ZX09735-001,Ming-Wei Wang and 2018ZX09711002-002-005,Dehua Yang)and the Novo Nordisk-CAS Research Fund(NNCAS-2017-1CC to Dehua Yang)。
文摘Receptor activity-modulating proteins(RAMPs)are accessory molecules that form complexes with specific G protein-coupled receptors(GPCRs)and modulate their functions.It is established that RAMP interacts with the glucagon receptor family of GPCRs but the underlying mechanism is poorly understood.In this study,we used a bioluminescence resonance energy transfer(BRET)approach to comprehensively investigate such interactions.In conjunction with c AMP accumulation,Gaqactivation andβ-arrestin1/2 recruitment assays,we not only verified the GPCR-RAMP pairs previously reported,but also identified new patterns of GPCR-RAMP interaction.While RAMP1 was able to modify the three signaling events elicited by both glucagon receptor(GCGR)and glucagon-like peptide-1 receptor(GLP-1 R),and RAMP2 mainly affectedβ-arrestin1/2 recruitment by GCGR,GLP-1 R and glucagon-like peptide-2 receptor,RAMP3 showed a widespread negative impact on all the family members except for growth hormone-releasing hormone receptor covering the three pathways.Our results suggest that RAMP modulates both G protein dependent and independent signal transduction among the glucagon receptor family members in a receptor-specific manner.Mapping such interactions provides new insights into the role of RAMP in ligand recognition and receptor activation.
