While severe acute respiratory syndrome coronavirus （SARS-CoV）~as initially thought to enter cells through direct fusion with the plasma membrane, more recent evidence suggests that yirus entry may also involve endo...While severe acute respiratory syndrome coronavirus （SARS-CoV）~as initially thought to enter cells through direct fusion with the plasma membrane, more recent evidence suggests that yirus entry may also involve endocytosis. We have found that SARS-CoV enters cells viapH- and receptor-dependent endocytosis. Treatment of cells with either SARS-COV spike protein or spike-bearing pseudoviruses resulted in the translocation of angiotensin-converting enzyme 2 （ACE2）, the functional receptor of SARS-CoV, from the cell surface to endosomes. In addition, the spike-bearing pseudoviruses and early endosome antigen 1 were found to colocalize in endosomes. Further analyses using specific endocytic path- way inhibitors and dominant-negative Epsl5 as well as caveolin-1 colocalization study suggested that virus entry was mediated by a clathrin- and caveolae-independent mechanism. Moreover, cholesterol- and sphingolipid-rich lipid raft microdomains in the plasma membrane, which have been shown to act as platforms for many physiological signaling pathways, were shown to be involved in virus entry. Endocytic entry of SARS-CoV may expand the cellular range of SARS-CoV infection, and our findings here contribute to the understanding of SARS-CoV pathogenesis, providing new information for anti-viral drug research.展开更多
Endocytosis occurs at the cell surface and involves internalization of the plasma membrane （PM） along with its constituent membrane proteins and lipids. Endocytosis is involved in sampling of the extracellular milie...Endocytosis occurs at the cell surface and involves internalization of the plasma membrane （PM） along with its constituent membrane proteins and lipids. Endocytosis is involved in sampling of the extracellular milieu and also serves to regulate various processes initiated at the cell surface. These include nutrient uptake, signaling from cell- surface receptors, and many other processes essential for cell and tissue functioning in metazoans. It is also central to the maintenance of PM lipid and protein homeostasis. There are multiple means of internalization that operate concurrently, at the cell surface. With advancement in high-resolution visualization techniques, it is now possible to track multiple endocytic cargo at the same time, revealing a remarkable diversity of endocytic processes in a single cell. A combination of live cell imaging and efficient genetic manipulations has also aided in understanding the functional hierarchy of molecular players in these mechanisms of internalization. Here we provide an account of various endocytic routes, their mechanisms of operation and occurrence across phyla.展开更多
Transforming growth factor-β （TGF-β） signaling is tightly regulated to ensure its proper physiological functions in different cells and tissues. Like other cell surface receptors, TGF-β receptors are internalized...Transforming growth factor-β （TGF-β） signaling is tightly regulated to ensure its proper physiological functions in different cells and tissues. Like other cell surface receptors, TGF-β receptors are internalized into the cell, and this process plays an important regulatory role in TGF-β signaling. It is well documented that TGF-β receptors are endocytosed via clathrin-coated vesicles as TGF-β endocytosis can be blocked by potassium depletion and the GTPasedeficient dynamin K44A mutant. TGF-β receptors may also enter cells via cholesterol-rich membrane microdomain lipid rafts/caveolae and are found in caveolin-l-positive vesicles. Although receptor endocytosis is not essential for TGF-β signaling, clathrin-mediated endocytosis has been shown to promote TGF-β-induced Smad activation and transcriptional responses. Lipid rafts/caveolae are widely regarded as signaling centers for G protein-coupled recep- tors and tyrosine kinase receptors, but they are indicated to facilitate the degradation of TGF-β receptors and there- fore turnoff of TGF-β signaling. This review summarizes current understanding of TGF-β receptor endocytosis, the possible mechanisms underlying this process, and the role of endocytosis in modulation of TGF-β signaling.展开更多
The human hepatitis B virus （HBV） and the duck hepatitis B virus （DHBV） share several fundamental features. Both viruses have a partially double-stranded DNA genome that is replicated via a RNA intermediate and th...The human hepatitis B virus （HBV） and the duck hepatitis B virus （DHBV） share several fundamental features. Both viruses have a partially double-stranded DNA genome that is replicated via a RNA intermediate and the coding open reading frames （ORFs） overlap extensively. In addition, the genomic and structural organization, as well as replication and biological characteristics, are very similar in both viruses. Host of the key features of hepadnaviral infection were first discovered in the DHBV model system and subsequently confirmed for HBV. There are, however, several differences between human HBV and DHBV. This review will focus on the molecular and cellular biology, evolution, and host adaptation of the avian hepatitis B viruses with particular emphasis on DHBV as a model system.展开更多
The major brassinosteroid （BR） receptor of Arabidopsis BRASSINOSTEROID INSENSITIVE1 （BRI1） plays fundamental roles in BR signaling, but the molecular mechanisms underlying the effects of BR on BRI1 internalization...The major brassinosteroid （BR） receptor of Arabidopsis BRASSINOSTEROID INSENSITIVE1 （BRI1） plays fundamental roles in BR signaling, but the molecular mechanisms underlying the effects of BR on BRI1 internalization and assembly state remain unclear. Here, we applied variable angle total internal reflection fluorescence microscopy and fluorescence cross-correlation spectroscopy to analyze the dynamics of GFP-tagged BRII. We found that, in response to BR, the degree of co-localization of BRI1-GFP with AtFIotl-mCherry increased, and especially BR stimulated the membrane microdomain-associated pathway of BRI1 internalization. We also verified these observations in endocytosis-defective chc2-1 mutants and the AtFIotl amiRNA 15-5 lines. Furthermore, examination of the phosphorylation status of bril-EMS-suppressor 1 and measurement of BR-responsive gene expression revealed that membrane microdomains affect BR signaling. These results suggest that BR promotes the partitioning of BRI1 into functional membrane microdomains to activate BR signaling.展开更多
Influenza A virus H5N1 presents a major threat to human health. The entry of influenza virus into host cells is believed to be mediated by hemagglutinin (HA), a virus surface glycoprotein that can bind terminal sialic...Influenza A virus H5N1 presents a major threat to human health. The entry of influenza virus into host cells is believed to be mediated by hemagglutinin (HA), a virus surface glycoprotein that can bind terminal sialic acid residues on host cell glycoproteins and glycolipids. In this study, we elucidated the pathways through which H5N1 enters human lung carcinoma cell line A549. We first proved that H5N1 can enter A549 cells via endocytosis, as lysosomotropic agents, such as bafilomycin A1 and chloroquine, can rescue H5N1-induced A549 cell death. By using specific inhibitors, and siRNAs that target the clathrin pathway, we further found that H5N1 could enter A549 cells via clathrin-mediated endocytosis, while inhibitors targeting caveolae-mediated endocytosis could not inhibit H5N1 cell entry. These findings expand our understanding of H5N1 pathogenesis and provide new information for anti-viral drug research.展开更多
稀土在工业、医药领域、基础研究以及在我国的广泛农用引起了人们对其生物效应机理以及可能毒性的关注.在稀土生物学效应机理及毒性的研究中,无论是在动物水平还是细胞层次,引起生物学效应的稀土物种都是一个关键问题,一直存在争议.本...稀土在工业、医药领域、基础研究以及在我国的广泛农用引起了人们对其生物效应机理以及可能毒性的关注.在稀土生物学效应机理及毒性的研究中,无论是在动物水平还是细胞层次,引起生物学效应的稀土物种都是一个关键问题,一直存在争议.本文对以动物、细胞为模型的生物效应研究中的实验条件进行分析,对生理条件下引起稀土生物学效应的可能物种提出"稀土离子池"(rare earth ion pool)模型,并对其引起生物学效应的活性物种以及与细胞膜相互作用的方式进行了探讨,以期为阐明复杂生物学体系中稀土化合物的作用机制提供思路.展开更多
Plants employ sophisticated mechanisms to interact with pathogenic as well as beneficial microbes. Of those, membrane trafficking is key in establishing a rapid and precise response. Upon interaction with pathogenic m...Plants employ sophisticated mechanisms to interact with pathogenic as well as beneficial microbes. Of those, membrane trafficking is key in establishing a rapid and precise response. Upon interaction with pathogenic microbes, surface-localized immune receptors undergo endocytosis for signal transduction and activity regulation while cell wall components, antimicrobial compounds, and defense proteins are delivered to pathogen invasion sites through polarized secretion. To sustain mutualistic associations, host cells also reprogram the membrane trafficking system to accommodate invasive structures of symbi- otic microbes. Here, we provide an analysis of recent advances in understanding the roles of secretory and endocytic membrane trafficking pathways in plant immune activation. We also discuss strategies deployed by adapted microbes to manipulate these pathways to subvert or inhibit plant defense.展开更多
Nanomedicines employ multiple endocytic pathways to enter cells.Their following fate is interesting,but it is not sufficient understood currently.This review introduces the endocytic pathways,presents new technologies...Nanomedicines employ multiple endocytic pathways to enter cells.Their following fate is interesting,but it is not sufficient understood currently.This review introduces the endocytic pathways,presents new technologies to confirm the specific endocytic pathways and discusses factors for pathway selection.In addition,some intriguing implication about nanomedicine design based on endocytosis will also be discussed at the end.This review may provide new thoughts for the design of novel multifunctional nanomedicines.展开更多
文摘While severe acute respiratory syndrome coronavirus （SARS-CoV）~as initially thought to enter cells through direct fusion with the plasma membrane, more recent evidence suggests that yirus entry may also involve endocytosis. We have found that SARS-CoV enters cells viapH- and receptor-dependent endocytosis. Treatment of cells with either SARS-COV spike protein or spike-bearing pseudoviruses resulted in the translocation of angiotensin-converting enzyme 2 （ACE2）, the functional receptor of SARS-CoV, from the cell surface to endosomes. In addition, the spike-bearing pseudoviruses and early endosome antigen 1 were found to colocalize in endosomes. Further analyses using specific endocytic path- way inhibitors and dominant-negative Epsl5 as well as caveolin-1 colocalization study suggested that virus entry was mediated by a clathrin- and caveolae-independent mechanism. Moreover, cholesterol- and sphingolipid-rich lipid raft microdomains in the plasma membrane, which have been shown to act as platforms for many physiological signaling pathways, were shown to be involved in virus entry. Endocytic entry of SARS-CoV may expand the cellular range of SARS-CoV infection, and our findings here contribute to the understanding of SARS-CoV pathogenesis, providing new information for anti-viral drug research.
文摘Endocytosis occurs at the cell surface and involves internalization of the plasma membrane （PM） along with its constituent membrane proteins and lipids. Endocytosis is involved in sampling of the extracellular milieu and also serves to regulate various processes initiated at the cell surface. These include nutrient uptake, signaling from cell- surface receptors, and many other processes essential for cell and tissue functioning in metazoans. It is also central to the maintenance of PM lipid and protein homeostasis. There are multiple means of internalization that operate concurrently, at the cell surface. With advancement in high-resolution visualization techniques, it is now possible to track multiple endocytic cargo at the same time, revealing a remarkable diversity of endocytic processes in a single cell. A combination of live cell imaging and efficient genetic manipulations has also aided in understanding the functional hierarchy of molecular players in these mechanisms of internalization. Here we provide an account of various endocytic routes, their mechanisms of operation and occurrence across phyla.
基金The work in Ye-Guang Chen＇s laboratory is supported by grants from the National Natural Science Foundation of China （30430360, 30671033） and the Ministry of Sciences and Technology of China 973 Program （2004CB720002, 2006CB943401, 2006CB910102） and 863 Program （2006AA02Z 172）.
文摘Transforming growth factor-β （TGF-β） signaling is tightly regulated to ensure its proper physiological functions in different cells and tissues. Like other cell surface receptors, TGF-β receptors are internalized into the cell, and this process plays an important regulatory role in TGF-β signaling. It is well documented that TGF-β receptors are endocytosed via clathrin-coated vesicles as TGF-β endocytosis can be blocked by potassium depletion and the GTPasedeficient dynamin K44A mutant. TGF-β receptors may also enter cells via cholesterol-rich membrane microdomain lipid rafts/caveolae and are found in caveolin-l-positive vesicles. Although receptor endocytosis is not essential for TGF-β signaling, clathrin-mediated endocytosis has been shown to promote TGF-β-induced Smad activation and transcriptional responses. Lipid rafts/caveolae are widely regarded as signaling centers for G protein-coupled recep- tors and tyrosine kinase receptors, but they are indicated to facilitate the degradation of TGF-β receptors and there- fore turnoff of TGF-β signaling. This review summarizes current understanding of TGF-β receptor endocytosis, the possible mechanisms underlying this process, and the role of endocytosis in modulation of TGF-β signaling.
基金Supported by the Freie und Hansestadt Hamburg and the Bundesministcrium für Gesundheit und Soziale Sicherung grants from DFG and by the German Competence Network for Viral Hepatitis （Hop-Net）, funded by the German Ministry of Education and Research （BMBF）, Grant No. TFI3. IWe apologize to those authors whose work we could not cite directly due to space limitations. The authors are indebted to Claudia Franke （Heinrich-Pette-Institute, Hamburg, Germany） for providing the picture of core protein phosphorylation.
文摘The human hepatitis B virus （HBV） and the duck hepatitis B virus （DHBV） share several fundamental features. Both viruses have a partially double-stranded DNA genome that is replicated via a RNA intermediate and the coding open reading frames （ORFs） overlap extensively. In addition, the genomic and structural organization, as well as replication and biological characteristics, are very similar in both viruses. Host of the key features of hepadnaviral infection were first discovered in the DHBV model system and subsequently confirmed for HBV. There are, however, several differences between human HBV and DHBV. This review will focus on the molecular and cellular biology, evolution, and host adaptation of the avian hepatitis B viruses with particular emphasis on DHBV as a model system.
文摘The major brassinosteroid （BR） receptor of Arabidopsis BRASSINOSTEROID INSENSITIVE1 （BRI1） plays fundamental roles in BR signaling, but the molecular mechanisms underlying the effects of BR on BRI1 internalization and assembly state remain unclear. Here, we applied variable angle total internal reflection fluorescence microscopy and fluorescence cross-correlation spectroscopy to analyze the dynamics of GFP-tagged BRII. We found that, in response to BR, the degree of co-localization of BRI1-GFP with AtFIotl-mCherry increased, and especially BR stimulated the membrane microdomain-associated pathway of BRI1 internalization. We also verified these observations in endocytosis-defective chc2-1 mutants and the AtFIotl amiRNA 15-5 lines. Furthermore, examination of the phosphorylation status of bril-EMS-suppressor 1 and measurement of BR-responsive gene expression revealed that membrane microdomains affect BR signaling. These results suggest that BR promotes the partitioning of BRI1 into functional membrane microdomains to activate BR signaling.
基金Supported by the National Natural Science Foundation of China (Grant No. 30623009)National Basic Research Program of China (Grant No. 2005CB523000)
文摘Influenza A virus H5N1 presents a major threat to human health. The entry of influenza virus into host cells is believed to be mediated by hemagglutinin (HA), a virus surface glycoprotein that can bind terminal sialic acid residues on host cell glycoproteins and glycolipids. In this study, we elucidated the pathways through which H5N1 enters human lung carcinoma cell line A549. We first proved that H5N1 can enter A549 cells via endocytosis, as lysosomotropic agents, such as bafilomycin A1 and chloroquine, can rescue H5N1-induced A549 cell death. By using specific inhibitors, and siRNAs that target the clathrin pathway, we further found that H5N1 could enter A549 cells via clathrin-mediated endocytosis, while inhibitors targeting caveolae-mediated endocytosis could not inhibit H5N1 cell entry. These findings expand our understanding of H5N1 pathogenesis and provide new information for anti-viral drug research.
文摘稀土在工业、医药领域、基础研究以及在我国的广泛农用引起了人们对其生物效应机理以及可能毒性的关注.在稀土生物学效应机理及毒性的研究中,无论是在动物水平还是细胞层次,引起生物学效应的稀土物种都是一个关键问题,一直存在争议.本文对以动物、细胞为模型的生物效应研究中的实验条件进行分析,对生理条件下引起稀土生物学效应的可能物种提出"稀土离子池"(rare earth ion pool)模型,并对其引起生物学效应的活性物种以及与细胞膜相互作用的方式进行了探讨,以期为阐明复杂生物学体系中稀土化合物的作用机制提供思路.
文摘Plants employ sophisticated mechanisms to interact with pathogenic as well as beneficial microbes. Of those, membrane trafficking is key in establishing a rapid and precise response. Upon interaction with pathogenic microbes, surface-localized immune receptors undergo endocytosis for signal transduction and activity regulation while cell wall components, antimicrobial compounds, and defense proteins are delivered to pathogen invasion sites through polarized secretion. To sustain mutualistic associations, host cells also reprogram the membrane trafficking system to accommodate invasive structures of symbi- otic microbes. Here, we provide an analysis of recent advances in understanding the roles of secretory and endocytic membrane trafficking pathways in plant immune activation. We also discuss strategies deployed by adapted microbes to manipulate these pathways to subvert or inhibit plant defense.
文摘Nanomedicines employ multiple endocytic pathways to enter cells.Their following fate is interesting,but it is not sufficient understood currently.This review introduces the endocytic pathways,presents new technologies to confirm the specific endocytic pathways and discusses factors for pathway selection.In addition,some intriguing implication about nanomedicine design based on endocytosis will also be discussed at the end.This review may provide new thoughts for the design of novel multifunctional nanomedicines.
