Plants' developmental plasticity plays a pivotal role in responding to environmental conditions. One of the most plastic plant organs is the root system. Different environmental stimuli such as nutrients and water de...Plants' developmental plasticity plays a pivotal role in responding to environmental conditions. One of the most plastic plant organs is the root system. Different environmental stimuli such as nutrients and water deficiency may induce lateral root formation to compensate for a low level of water and/or nutrients. It has been shown that the hor- mone auxin tunes lateral root development and components for its signaling pathway have been identified. Using chemi- cal biology, we discovered an Arabidopsis thaliana lateral root formation mechanism that is independent of the auxin receptor SCFTM. The bioactive compound Sortin2 increased lateral root occurrence by acting upstream from the morpho- logical marker of lateral root primordium formation, the mitotic activity. The compound did not display auxin activity. At the cellular level, Sortin2 accelerated endosomal trafficking, resulting in increased trafficking of plasma membrane recy- cling proteins to the vacuole. Sortin2 affected Late endosome/PVC/MVB trafficking and morphology. Combining Sortin2 with well-known drugs showed that endocytic trafficking of Late E/PVC/MVB towards the vacuole is pivotal for Sortin2- induced SCFTm-independent lateral root initiation. Our results revealed a distinctive role for endosomal trafficking in the promotion of lateral root formation via a process that does not rely on the auxin receptor complex SCFTM.展开更多
ACAP1, a GTPase-activating protein (GAP) for ADP-ribosylation factor (ARF) 6, is part of a novel clathrin coat complex that is regulated by ARF6 for endocytic recycling in
In this paper, the relatived mechanism between lipofectamine 2000 mediated transmembrane gene delivery and endocytic pathway were investigated. Clathrin and caveolae-mediated endocytic pathway contributions to transfe...In this paper, the relatived mechanism between lipofectamine 2000 mediated transmembrane gene delivery and endocytic pathway were investigated. Clathrin and caveolae-mediated endocytic pathway contributions to transfection efficiency were studied. The inhibitors of endocytosis were used to treat HEp-2 cells before lipofectamine 2000/pGFP-N2 transfection. Transfection efficiency was evaluated with green fluorescence protein (GFP) expression assays. Cell viability and cytotoxicity were evaluated with MTT method. The results indicated that inhibitors of clathrin (chlorpromazine or wortmannin) and caveolin (genistein) could reduce the cell transfection efficiency observably. Both clathrin and caveolae-mediated endocytic pathways play important roles in transmembrane gene delivery.展开更多
Morphine is a schedule II-controlled substance that used to allow the diminution of intra-operative, post-operative orchronic pain. However, its usage is limited due to addiction and overdose liabilities. Morphine was...Morphine is a schedule II-controlled substance that used to allow the diminution of intra-operative, post-operative orchronic pain. However, its usage is limited due to addiction and overdose liabilities. Morphine was observed to cause tolerance,dependence and withdrawal in human. Justification: to date lack of scientific evidence of morphine addiction was carried out byusing specific single human neuroblastoma cell-line (SK-N-SH). Therefore, this study was performed to establish the morphineaddiction model in this cell line. The cells were exposed to morphine for 24 hrs before treatment with methadone, as ananti-withdrawal drug for subsequence 24 hours. The cytosolic fraction of the cell was used in different objectives including receptoraffinity, withdrawal properties, endocytic machinery, desensitisation or internalisation and cellular adaptation. The result shows thatmorphine and methadone bind to the μ-opioid receptor. The morphine-treated cells were observed to increase the expression ofaddiction markers, have a low rate of the endocytic machinery, cause desensitisation of receptor and reduce cellular adaptation.Those changes by morphine were normalised by the treatment of methadone. As a whole, it is postulated that neuroblastoma cell line,SK-N-SH, can be used as an in-vitro model to demonstrate morphine addiction before animal and human testing.展开更多
Cytomegaloviruses (CMVs), members of the herpesvirus family, have evolved a variety of mechanisms to evade the immune response to survive in infected hosts and to establish latent infection, They effectively hide in...Cytomegaloviruses (CMVs), members of the herpesvirus family, have evolved a variety of mechanisms to evade the immune response to survive in infected hosts and to establish latent infection, They effectively hide infected cells from the effector mechanisms of adaptive immunity by eliminating cellular proteins (major histocompatibility Class I and Class II molecules) from the cell surface that display viral antigens to CD8 and CD4 T lymphocytes, CMVs also successfully escape recognition and elimination of infected cells by natural killer (NK) cells, effector cells of innate immunity, either by mimicking NK cell inhibitory ligands or by downregulating NK cell-activating ligands, To accomplish these immunoevasion functions, CMVs encode several proteins that function in the biosynthetic pathway by inhibiting the assembly and trafficking of cellular proteins that participate in immune recognition and thereby, block their appearance at the cell surface, However, elimination of these proteins from the cell surface can also be achieved by perturbation of their endosomal route and subsequent relocation from the cell surface into intracellular compartments, Namely, the physiological route of every cellular protein, including immune recognition molecules, is characterized by specific features that determine its residence time at the cell surface, In this review, we summarize the current understanding of endocytic trafficking of immune recognition molecules and perturbations of the endosomal system during infection with CMVs and other members of the herpesvirus family that contribute to their immune evasion mechanisms,展开更多
Plants have evolved a sophisticated immune system to fight against pathogenic microbes. Upon detection of pathogen invasion by immune receptors, the immune system is turned on, resulting in production of antimicrobial...Plants have evolved a sophisticated immune system to fight against pathogenic microbes. Upon detection of pathogen invasion by immune receptors, the immune system is turned on, resulting in production of antimicrobial molecules including pathogenesis-related(PR) proteins.Conceivably, an efficient immune response depends on the capacity of the plant cell's protein/membrane trafficking network to deploy the right defense-associated molecules in the right place at the right time. Recent research in this area shows that while the abundance of cell surface immune receptors is regulated by endocytosis, many intracellular immune receptors, when activated, are partitioned between the cytoplasm and the nucleus for induction of defense genes and activation of programmed cell death, respectively. Vesicle transport is an essential process for secretion of PR proteins to the apoplastic space and targeting of defense-related proteins to the plasma membrane or other endomembrane compartments. In this review, we discuss the various aspects of protein trafficking during plant immunity, with a focus on the immunity proteins on the move and the major components of the trafficking machineries engaged.展开更多
文摘Plants' developmental plasticity plays a pivotal role in responding to environmental conditions. One of the most plastic plant organs is the root system. Different environmental stimuli such as nutrients and water deficiency may induce lateral root formation to compensate for a low level of water and/or nutrients. It has been shown that the hor- mone auxin tunes lateral root development and components for its signaling pathway have been identified. Using chemi- cal biology, we discovered an Arabidopsis thaliana lateral root formation mechanism that is independent of the auxin receptor SCFTM. The bioactive compound Sortin2 increased lateral root occurrence by acting upstream from the morpho- logical marker of lateral root primordium formation, the mitotic activity. The compound did not display auxin activity. At the cellular level, Sortin2 accelerated endosomal trafficking, resulting in increased trafficking of plasma membrane recy- cling proteins to the vacuole. Sortin2 affected Late endosome/PVC/MVB trafficking and morphology. Combining Sortin2 with well-known drugs showed that endocytic trafficking of Late E/PVC/MVB towards the vacuole is pivotal for Sortin2- induced SCFTm-independent lateral root initiation. Our results revealed a distinctive role for endosomal trafficking in the promotion of lateral root formation via a process that does not rely on the auxin receptor complex SCFTM.
文摘ACAP1, a GTPase-activating protein (GAP) for ADP-ribosylation factor (ARF) 6, is part of a novel clathrin coat complex that is regulated by ARF6 for endocytic recycling in
文摘In this paper, the relatived mechanism between lipofectamine 2000 mediated transmembrane gene delivery and endocytic pathway were investigated. Clathrin and caveolae-mediated endocytic pathway contributions to transfection efficiency were studied. The inhibitors of endocytosis were used to treat HEp-2 cells before lipofectamine 2000/pGFP-N2 transfection. Transfection efficiency was evaluated with green fluorescence protein (GFP) expression assays. Cell viability and cytotoxicity were evaluated with MTT method. The results indicated that inhibitors of clathrin (chlorpromazine or wortmannin) and caveolin (genistein) could reduce the cell transfection efficiency observably. Both clathrin and caveolae-mediated endocytic pathways play important roles in transmembrane gene delivery.
文摘Morphine is a schedule II-controlled substance that used to allow the diminution of intra-operative, post-operative orchronic pain. However, its usage is limited due to addiction and overdose liabilities. Morphine was observed to cause tolerance,dependence and withdrawal in human. Justification: to date lack of scientific evidence of morphine addiction was carried out byusing specific single human neuroblastoma cell-line (SK-N-SH). Therefore, this study was performed to establish the morphineaddiction model in this cell line. The cells were exposed to morphine for 24 hrs before treatment with methadone, as ananti-withdrawal drug for subsequence 24 hours. The cytosolic fraction of the cell was used in different objectives including receptoraffinity, withdrawal properties, endocytic machinery, desensitisation or internalisation and cellular adaptation. The result shows thatmorphine and methadone bind to the μ-opioid receptor. The morphine-treated cells were observed to increase the expression ofaddiction markers, have a low rate of the endocytic machinery, cause desensitisation of receptor and reduce cellular adaptation.Those changes by morphine were normalised by the treatment of methadone. As a whole, it is postulated that neuroblastoma cell line,SK-N-SH, can be used as an in-vitro model to demonstrate morphine addiction before animal and human testing.
文摘Cytomegaloviruses (CMVs), members of the herpesvirus family, have evolved a variety of mechanisms to evade the immune response to survive in infected hosts and to establish latent infection, They effectively hide infected cells from the effector mechanisms of adaptive immunity by eliminating cellular proteins (major histocompatibility Class I and Class II molecules) from the cell surface that display viral antigens to CD8 and CD4 T lymphocytes, CMVs also successfully escape recognition and elimination of infected cells by natural killer (NK) cells, effector cells of innate immunity, either by mimicking NK cell inhibitory ligands or by downregulating NK cell-activating ligands, To accomplish these immunoevasion functions, CMVs encode several proteins that function in the biosynthetic pathway by inhibiting the assembly and trafficking of cellular proteins that participate in immune recognition and thereby, block their appearance at the cell surface, However, elimination of these proteins from the cell surface can also be achieved by perturbation of their endosomal route and subsequent relocation from the cell surface into intracellular compartments, Namely, the physiological route of every cellular protein, including immune recognition molecules, is characterized by specific features that determine its residence time at the cell surface, In this review, we summarize the current understanding of endocytic trafficking of immune recognition molecules and perturbations of the endosomal system during infection with CMVs and other members of the herpesvirus family that contribute to their immune evasion mechanisms,
基金supported by a grant from the National Science Foundation(grant number IOS-1146589)to S.X.Research in the Wang lab is supported by grants from the National Natural Science Foundation of China(grant numbers 31371931 and 31430072)to W.M.W
文摘Plants have evolved a sophisticated immune system to fight against pathogenic microbes. Upon detection of pathogen invasion by immune receptors, the immune system is turned on, resulting in production of antimicrobial molecules including pathogenesis-related(PR) proteins.Conceivably, an efficient immune response depends on the capacity of the plant cell's protein/membrane trafficking network to deploy the right defense-associated molecules in the right place at the right time. Recent research in this area shows that while the abundance of cell surface immune receptors is regulated by endocytosis, many intracellular immune receptors, when activated, are partitioned between the cytoplasm and the nucleus for induction of defense genes and activation of programmed cell death, respectively. Vesicle transport is an essential process for secretion of PR proteins to the apoplastic space and targeting of defense-related proteins to the plasma membrane or other endomembrane compartments. In this review, we discuss the various aspects of protein trafficking during plant immunity, with a focus on the immunity proteins on the move and the major components of the trafficking machineries engaged.