The Arabidopsis pi4kβ1,2 mutant is mutated in the phosphatidylinositol 4-kinase(PI4K)β1 and PI4Kβ2 enzymes which are involved in the biosynthesis of phosphatidylinositol 4-phosphate(PI4P),a minor membrane lipid wit...The Arabidopsis pi4kβ1,2 mutant is mutated in the phosphatidylinositol 4-kinase(PI4K)β1 and PI4Kβ2 enzymes which are involved in the biosynthesis of phosphatidylinositol 4-phosphate(PI4P),a minor membrane lipid with important signaling roles.pi4kβ1,2 plants display autoimmunity and shorter roots.Though the pi4kβ1,2 mutant has been extensively characterized,the source of its autoimmunity remains largely unknown.In this study,through a genetic suppressor screen,we identified multiple partial loss-of-function alleles of signal peptide peptidase(spp)that can suppress all the defects of pi4kβ1,2.SPP is an intramembrane cleaving aspartic protease.Interestingly,pi4kβ1,2 plants display enhanced ER stress response and mutations in SPP can suppress such phenotype.Furthermore,reduced ER stress responses were observed in the spp single mutants.Overall,our study reveals a previously unknown function of PI4Kβand SPP in ER stress and plant immunity.展开更多
Epidemiological studies have indicated that branched-chain amino acids(BCAAs)increased and gut microbiota disordered in type 2 diabetes mellitus(T2DM).This study aimed to investigate the mechanism of Lactiplantibacill...Epidemiological studies have indicated that branched-chain amino acids(BCAAs)increased and gut microbiota disordered in type 2 diabetes mellitus(T2DM).This study aimed to investigate the mechanism of Lactiplantibacillus plantarum strain 84-3(Lp84-3)combined with Staphylococcus aureus bacteriophage on ameliorating T2DM.Here we perform a case-control study and identify that Staphylococcus_phage was inversely correlated with fasting blood glucose(FBG).It revealed that Lp84-3 could inhibit the growth of S.aureus,and Lp84-3 contains BCAAs degradation enzymes in its genome.Furthermore,Lp84-3 alone or combined with S.aureus bacteriophage interventions can improve blood glucose,insulin resistance,triglycerides,interleukin-1β,tumor necrosis factor-α(TNF-α),BCAAs,and acetyllactate synthase(ALS)in db/db mice.Lp84-3 and S.aureus bacteriophage decreased S.aureus,Malacoplasma iowae,and Oscillibacter sp.,and increased some beneficial such as L.plantarum and Muribaculaceae bacterium.Transcriptomic analyses revealed that Lp84-3 and S.aureus bacteriophage activated the PI3K/AKT/GLUT4 signaling pathway and upregulated key genes of Il22,Hgf,Col6a1,Gh,Itga10,Fgf23,and Prl involved in glucose metabolism in hypothalamus.Collectively,Lp84-3 and S.aureus bacteriophage alleviate T2DM by modulating gut microbiota and enhancing glucose metabolism in hypothalamus,supporting its potential use as a promising functional compound microecological agent for alleviating T2DM.展开更多
基金supported by grants to XL from the National Sciences and Engineering Research Council(NSERC)Discovery programthe NSERCCREATE funded Plant Responses To Eliminate Critical Threats(PRoTECT)program,Canada Research Chairs(CRC)the Canadian Foundation for Innovation(CFI),and scholarships to KTD from the Izaak Walton Killam Memorial Fund of the Killam Trusts and The University of British Columbia’s Four Year Fellowship program。
文摘The Arabidopsis pi4kβ1,2 mutant is mutated in the phosphatidylinositol 4-kinase(PI4K)β1 and PI4Kβ2 enzymes which are involved in the biosynthesis of phosphatidylinositol 4-phosphate(PI4P),a minor membrane lipid with important signaling roles.pi4kβ1,2 plants display autoimmunity and shorter roots.Though the pi4kβ1,2 mutant has been extensively characterized,the source of its autoimmunity remains largely unknown.In this study,through a genetic suppressor screen,we identified multiple partial loss-of-function alleles of signal peptide peptidase(spp)that can suppress all the defects of pi4kβ1,2.SPP is an intramembrane cleaving aspartic protease.Interestingly,pi4kβ1,2 plants display enhanced ER stress response and mutations in SPP can suppress such phenotype.Furthermore,reduced ER stress responses were observed in the spp single mutants.Overall,our study reveals a previously unknown function of PI4Kβand SPP in ER stress and plant immunity.
基金supported by research grants from the Guangdong Province Basic and Applied Basic Research Fund Project(2022A1515110447)Open Fund Project of the State Key Laboratory of Applied Microbiology in South China(SKLAM006-2022)+1 种基金74th batch of general funding from the China Postdoctoral Science Foundation(2023M740774)Guangdong Provincial People’s Hospital,Postdoctoral Research Launch Fund(BY012022017)。
文摘Epidemiological studies have indicated that branched-chain amino acids(BCAAs)increased and gut microbiota disordered in type 2 diabetes mellitus(T2DM).This study aimed to investigate the mechanism of Lactiplantibacillus plantarum strain 84-3(Lp84-3)combined with Staphylococcus aureus bacteriophage on ameliorating T2DM.Here we perform a case-control study and identify that Staphylococcus_phage was inversely correlated with fasting blood glucose(FBG).It revealed that Lp84-3 could inhibit the growth of S.aureus,and Lp84-3 contains BCAAs degradation enzymes in its genome.Furthermore,Lp84-3 alone or combined with S.aureus bacteriophage interventions can improve blood glucose,insulin resistance,triglycerides,interleukin-1β,tumor necrosis factor-α(TNF-α),BCAAs,and acetyllactate synthase(ALS)in db/db mice.Lp84-3 and S.aureus bacteriophage decreased S.aureus,Malacoplasma iowae,and Oscillibacter sp.,and increased some beneficial such as L.plantarum and Muribaculaceae bacterium.Transcriptomic analyses revealed that Lp84-3 and S.aureus bacteriophage activated the PI3K/AKT/GLUT4 signaling pathway and upregulated key genes of Il22,Hgf,Col6a1,Gh,Itga10,Fgf23,and Prl involved in glucose metabolism in hypothalamus.Collectively,Lp84-3 and S.aureus bacteriophage alleviate T2DM by modulating gut microbiota and enhancing glucose metabolism in hypothalamus,supporting its potential use as a promising functional compound microecological agent for alleviating T2DM.
