Lipid rafts are sterol and sphingolipid rich membrane domains that possibly may play roles in multiple cellular processes. These domains are still the matter of debate and it is still unknown by which mechanism if any...Lipid rafts are sterol and sphingolipid rich membrane domains that possibly may play roles in multiple cellular processes. These domains are still the matter of debate and it is still unknown by which mechanism if any and organisms promote their formation. This study centers on the ease of in vitro formation of lipid rafts-like structures as it relates to the relative availability of sphingolipids, phospholipids, cholesterol, and membrane proteins. Following a 12 h incubation period, isolation and extraction of the lipid rafts-like assemblies, the composition of the structures was evaluated using HPLC. Cholesterol and sphingomyelin were detected at 206 nm and phosphatidylcholine was detected at 254 nm. Identification of lactose permease, a typical membrane protein, was done using FTIR. The thermal stability of the produced structures was also determined. Results show that the addition of cholesterol significantly increased both the amount of insoluble lipid rafts-like structures and their stability, and that the availability of a minimum amount of sphingolipid was necessary to produce larger amounts of more stable structures. However, the addition of phospholipids hindered the formation of lipid rafts-like assemblies and those formed were generally less stable.展开更多
Emodin [1,3,8-Trihydroxy-6-methylanthraquinone] has been reported to exhibit vascular anti-inflammatory properties.However,the relevant anti-inflammatory mechanisms are not well understood.The present study was design...Emodin [1,3,8-Trihydroxy-6-methylanthraquinone] has been reported to exhibit vascular anti-inflammatory properties.However,the relevant anti-inflammatory mechanisms are not well understood.The present study was design to explore the molecular target(s) of emodin展开更多
Background:Cotton fiber is a single-celled seed trichome that originates from the ovule epidermis.It is an excellent model for studying cell elongation.Along with the elongation of cotton fiber cell,the plasma membran...Background:Cotton fiber is a single-celled seed trichome that originates from the ovule epidermis.It is an excellent model for studying cell elongation.Along with the elongation of cotton fiber cell,the plasma membrane is also extremely expanded.Despite progress in understanding cotton fiber cell elongation,knowledge regarding the relationship of plasma membrane in cotton fiber cell development remains elusive.Methods:The plasma membrane of cotton fiber cells was marked with a low toxic fluorescent dye,di-4-ANEPPDHQ,at different stages of development.Fluorescence images were obtained using a confocal laser scanning microscopy.Subsequently,we investigated the relationship between lipid raft activity and cotton fiber development by calculating generalized polarization(GP values)and dual-channel ratio imaging.Results:We demonstrated that the optimum dyeing conditions were treatment with 3μmol·L-1 di-4-ANEPPDHQ for 5 min at room temperature,and the optimal fluorescence images were obtained with 488 nm excitation and500–580 nm and 620–720 nm dual channel emission.First,we examined lipid raft organization in the course of fiber development.The GP values were high in the fiber elongation stage(5–10 DPA,days past anthesis)and relatively low in the initial(0 DPA),secondary cell wall synthesis(20 DPA),and stable synthesis(30 DPA)stages.The GP value peaked in the 10 DPA fiber,and the value in 30 DPA fiber was the lowest.Furthermore,we examined the differences in lipid raft activity in fiber cells between the short fiber cotton mutant,Li-1,and its wild-type.The GP values of the Li-1 mutant fiber were lower than those of the wild type fiber at the elongation stage,and the GP values of 10 DPA fibers were lower than those of 5 DPA fibers in the Li-1 mutant.Conclusions:We established a system for examining membrane lipid raft activity in cotton fiber cells.We verified that lipid raft activity exhibited a low-high-low change regularity during the development of cotton fiber cell,and the pattern was disrupted in the short lint fiber Li-1 mutant,suggesting that membrane lipid order and lipid raft activity are closely linked to fiber cell development.展开更多
Amyloid-beta peptide is the main component of amyloid plaques,which are found in Alzheimer’s disease.The generation and deposition of amyloid-beta is one of the crucial factors for the onset and progression of Alzhei...Amyloid-beta peptide is the main component of amyloid plaques,which are found in Alzheimer’s disease.The generation and deposition of amyloid-beta is one of the crucial factors for the onset and progression of Alzheimer’s disease.Lipid rafts are glycolipid-rich liquid domains of the plasma membrane,where certain types of protein tend to aggregate and intercalate.Lipid rafts are involved in the generation of amyloid-beta oligomers and the formation of amyloid-beta peptides.In this paper,we review the mechanism by which lipid rafts disturb the aberrant degradative autophagic-lysosomal pathway of amyloid-beta,which plays an important role in the pathological process of Alzheimer’s disease.Moreover,we describe this mechanism from the view of the Two-system Theory of fasciology and thus,suggest that lipid rafts may be a new target of Alzheimer’s disease treatment.展开更多
GP64 is the major envelope glycoprotein associated with the budded virus (BV) of Autographa californica nucleopolyhedrovirus (AcMNPV) and is essential for attachment and budding of BV particles. Confocal microscopy an...GP64 is the major envelope glycoprotein associated with the budded virus (BV) of Autographa californica nucleopolyhedrovirus (AcMNPV) and is essential for attachment and budding of BV particles. Confocal microscopy and flotation assays established the presence of lipid raft domains within the plasma membranes of AcMNPV-infected Sf9 cells and suggested the association of GP64 with lipid rafts during infection. GP64 and filamentous actin (F-actin) were found to co-localise at the cell cortex at 24 and 48 hpi and an additional restructuring of F-actin during infection was visualised, resulting in a strongly polarised distribution of both F-actin and GP64 at the cell cortex. Depletion of F-actin, achieved by treatment of Sf9 cells with latrunculin B (LB), resulted in the redistribution of GP64 with significant cytoplasmic aggregation and reduced presence at the plasma membrane. Treatment with LB also resulted in reduced production of BV in Sf9 cells. Analysis of virus gene transcription confirmed this reduction was not due to decreased trafficking of nucleocapsids to the nucleus or to decreased production of infectious progeny nucleocapsids. Reduced BV production due to a lack of GP64 at the plasma membrane of AcMNPV-infected Sf9 cells treated with LB, suggests a key role for F-actin in the egress of BV.展开更多
Lipid rafts are cholesterol-enriched microdomains and implicated in many essential physiological ac-tivities such as the neurotransmitter release.Many studies have been carried out on the function of rafts inthe plasm...Lipid rafts are cholesterol-enriched microdomains and implicated in many essential physiological ac-tivities such as the neurotransmitter release.Many studies have been carried out on the function of rafts inthe plasma membranes,whereas little is known about the information of such microdomains in subcellularcompartments especially synaptic vesicles(SVs).In the well-studied plasma membranes,several proteinshave been recognized as raft markers,which are used to label or trace rafts.But the raft marker proteinon SVs has not been identified yet.Although some SV proteins,including VAMP and CPE,have beenfound in raft fractions,they cannot be used as markers due to their low abundance in rafts.In this work,we designed several chimera proteins and tested their characteristics for using as SV raft makers.First,we detected whether they located in SVs,and then the chimeras exhibiting the better localization in SVswere further examined for their enrichment in raft using detergent treatment and gradient density floatationanalysis.Our results indicate that one of the chimeric proteins is primarily located in SVs and distributedin raft microdomains,which strongly suggests that it could be served as a raft marker for SVs.展开更多
Cholesterol,as a common lipid on mammalian cell membranes,plays an important role in the formation of lipid rafts.Recent experiments suggest that the strength of cholesterol's regulation on lipid rafts can be affe...Cholesterol,as a common lipid on mammalian cell membranes,plays an important role in the formation of lipid rafts.Recent experiments suggest that the strength of cholesterol's regulation on lipid rafts can be affected by the length of the unsaturated phospholipid acyl chain on the membrane.In order to understand this observation,a simplified toy model containing three different molecules is proposed in this paper,where the tail length of phospholipids is considered.This model shows the regulation of membrane cholesterol on the phase separation of the lipid mixture and the formation of nano-domains,and also suggests that the configuration entropy of phospholipid tails is an essential factor.展开更多
Ebola virus(EBOV)is one of the most pathogenic viruses in humans which can cause a lethal hemorrhagic fever.Understanding the cellular entry mechanisms of EBOV can promote the development of new therapeutic strategies...Ebola virus(EBOV)is one of the most pathogenic viruses in humans which can cause a lethal hemorrhagic fever.Understanding the cellular entry mechanisms of EBOV can promote the development of new therapeutic strategies to control virus replication and spread.It has been known that EBOV virions bind to factors expressed at the host cell surface.Subsequently,the virions are internalized by a macropinocytosis-like process,followed by being trafficked through early and late endosomes.Recent researches indicate that the entry of EBOV into cells requires integrated and functional lipid rafts.Whilst lipid rafts have been hypothesized to play a role in virus entry,there is a current lack of supporting data.One major technical hurdle is the lack of effective approaches for observing viral entry.To provide evidence on the involvement of lipid rafts in the entry process of EBOV,we generated the fluorescently labeled Ebola virus like particles(VLPs),and utilized single-particle tracking(SPT)to visualize the entry of fluorescent Ebola VLPs in live cells and the interaction of Ebola VLPs with lipid rafts.In this study,we demonstrate the compartmentalization of Ebola VLPs in lipid rafts during entry process,and inform the essential function of lipid rafts for the entry of Ebola virus.As such,our study provides evidence to show that the raft integrity is critical for Ebola virus pathogenesis and that lipid rafts can serve as potential targets for the development of novel therapeutic strategies.展开更多
The first appearance of lipid rafts,or lipid rafts-like structure,was occasionally observed by cryo-electronic microscopy in 1980s as cavity,such as caveolae. However,the fully understanding of lipid raft was attribut...The first appearance of lipid rafts,or lipid rafts-like structure,was occasionally observed by cryo-electronic microscopy in 1980s as cavity,such as caveolae. However,the fully understanding of lipid raft was attributed by the studies of T cell activation,virus entry/budding,and other membrane events. During the interaction of T cell and antigen presenting cell,a highly organized structure is formed at the interface of the two cells,where cholesterol and sphingolipids are enriched,and form a liquid ordered phase that facilitates the signaling proteins on and off. Lipid rafts are also involved in virus entry and assembly. In this review,we will discuss cholesterol-sphingolipid floating microdomain,the lipid raft as a unique compartment of the plasma membrane,with biological functions that ensure correct intracellular traffic of proteins and lipids,such as protein-protein interactions by concentrating certain proteins in these microdomains,while excluding others. We also discuss the disruption of lipid rafts is related to different diseases and aging,and we especially exploit the lipid rafts as pharmaceutical targets for anti-virus and anti-inflammation,particularly a new approach to control HIV infection for AIDS prevention and protection by inhibition or disruption of lipid rafts.展开更多
Recent studies have shown that polyunsaturated fatty acids (PUFA) regulated the func-tions of membrane receptors in T cells and suppressed T cell -mediated immune responses. But the molecular mechanisms of immune regu...Recent studies have shown that polyunsaturated fatty acids (PUFA) regulated the func-tions of membrane receptors in T cells and suppressed T cell -mediated immune responses. But the molecular mechanisms of immune regulation are not yet elucidated. Lipid rafts are plasma membrane microdomains, in which many receptors localized. The purpose of this study was to investigate the effect of DHA on IL-2R signaling pathway in lipid rafts. We isolated lipid rafts by discontinuous sucrose density gradient ultracentrifugation, and found that DHA could change the composition of lipid rafts and alter the distribution of key molecules of IL-2R signaling pathway, which transferred from lipid rafts to detergent-soluble membrane fractions. These results revealed that DHA treatment increased the proportion of polyunsaturated fatty acids especially n?3 polyunsaturated fatty acids in lipid rafts and changed the lipid environment of membrane microdomains in T cells. Compared with controls, DHA changed the localization of IL-2R, STAT5a and STAT5b in lipid rafts and suppressed the expression of JAK1, JAK3 and tyrosine phosphotyrosine in soluble membrane fractions. Summarily, this study con-cluded the effects of DHA on IL-2R signaling pathway in lipid rafts and explained the regulation of PUFAs in T cell-mediated immune responses.展开更多
In this paper we report that the C2 domain of synaptotagmin I (syt I) could associate with lipid rafts of plasma membrane. We demonstrate that phosphatidylinositol 4,5-bisphosphate (PIP2) in the target membrane and Ca...In this paper we report that the C2 domain of synaptotagmin I (syt I) could associate with lipid rafts of plasma membrane. We demonstrate that phosphatidylinositol 4,5-bisphosphate (PIP2) in the target membrane and Ca2+ are the key factors to enhance the raft association of the C2 domain. We also found that the raft association of the C2 domain could be fulfilled by either C2A or C2B alone, suggesting that their raft association might be complementary. Finally, we indicate that destroying lipid rafts or blocking syt I-raft association could significantly reduce the Ca2+-driven release of glutamates. Our data indicate that the raft association of the C2 domain might play an important role in the regulated exocytosis.展开更多
For a long time, lipid rafts have been thought to participate in regulating neurotransmitter release. However,the existence of lipid rafts on synaptic vesicles (SVs) and the mechanism by which exocytosis-relative prot...For a long time, lipid rafts have been thought to participate in regulating neurotransmitter release. However,the existence of lipid rafts on synaptic vesicles (SVs) and the mechanism by which exocytosis-relative proteins distribute on this structure have not been fully investigated. There is also much controver-sial data concerning rafts on SVs and synaptic vesicle proteins which makes the results difficult to interpret. This study systematically analyzed the existence and properties of lipid rafts on purified SVs by sucrose density gradient centrifugation, cholesterol depletion, and temperature variation. The data reveals that typi-cal lipid rafts on SVs are both cholesterol dependent and temperature sensitive. Previous confusing results may have been caused by improper treatment or side effects of particular reagent. We also screened the lateral distribution of major exocytosis-related SV proteins and found that only the synaptobrevin (syb) and synaptotagmin (syt) produce detectable association with lipid rafts in 1% Triton X-100.展开更多
Reactive oxygen species(ROS) and oxidative stress are closely associated with the development of atherosclerosis,and the most important regulator of ROS production in endothelial cells is NADPH oxidase.Activation of N...Reactive oxygen species(ROS) and oxidative stress are closely associated with the development of atherosclerosis,and the most important regulator of ROS production in endothelial cells is NADPH oxidase.Activation of NADPH oxidase requires the assembly of multiple subunits into lipid rafts,which include specific lipid components,including free cholesterol and specific proteins.Disorders of lipid metabolism such as hyperlipidemia affect the cellular lipid components included in rafts,resulting in modification of cellular reactions that produce ROS.In the similar manner,several pathways associating ROS production are affected by the presence of lipid disorder through raft compartments.In this manuscript,we review the pathophysiological implications of hyperlipidemia and lipid rafts in the production of ROS.展开更多
Carbohydrates,lipids,and proteins are the three major nutrients required by the human body.The lipids,comprising triglycerides,phospholipids,and sterols,provide energy and essential fatty acids for the body,and are re...Carbohydrates,lipids,and proteins are the three major nutrients required by the human body.The lipids,comprising triglycerides,phospholipids,and sterols,provide energy and essential fatty acids for the body,and are required for the growth and maintenance of human cells and tissues.A variety of lipid molecules and their intermediates are involved in cell signaling and inflammation,and have been reported to promote tumor transformation and progression.Fatty acid biosynthetic enzymes are also involved in the lipid metabolism of tumors.Dyslipidemia is closely related to many solid tumors,and may both play a role in both tumorigenesis and be a consequence of tumor development.Therefore,abnormal lipid metabolism is strongly associated with tumor transformation and progression.This review discusses the signaling pathways,related genes,enzymes,and inflammatory cell factors involved in tumor lipid metabolism,as well as the roles of dyslipidemia in tumor transformation and progression.We believe the information provided will serve as valuable reference highlighting molecules that can be targeted to improve the treatment of tumors.展开更多
We investigate how an externally imposed curvature influences lipid segregation on two-phase-coexistent membranes.We show that the bending-modulus contrast of the two phases and the curvature act together to yield a r...We investigate how an externally imposed curvature influences lipid segregation on two-phase-coexistent membranes.We show that the bending-modulus contrast of the two phases and the curvature act together to yield a reduced effective line tension.On largely curved membranes,a state of multiple domains(or rafts) forms due to a mechanism analogous to that causing magnetic-vortex formation in type-II superconductors.We determine the criterion for such a multi-domain state to occur;we then calculate respectively the size of the domains formed on cylindrically and spherically curved membranes.展开更多
文摘Lipid rafts are sterol and sphingolipid rich membrane domains that possibly may play roles in multiple cellular processes. These domains are still the matter of debate and it is still unknown by which mechanism if any and organisms promote their formation. This study centers on the ease of in vitro formation of lipid rafts-like structures as it relates to the relative availability of sphingolipids, phospholipids, cholesterol, and membrane proteins. Following a 12 h incubation period, isolation and extraction of the lipid rafts-like assemblies, the composition of the structures was evaluated using HPLC. Cholesterol and sphingomyelin were detected at 206 nm and phosphatidylcholine was detected at 254 nm. Identification of lactose permease, a typical membrane protein, was done using FTIR. The thermal stability of the produced structures was also determined. Results show that the addition of cholesterol significantly increased both the amount of insoluble lipid rafts-like structures and their stability, and that the availability of a minimum amount of sphingolipid was necessary to produce larger amounts of more stable structures. However, the addition of phospholipids hindered the formation of lipid rafts-like assemblies and those formed were generally less stable.
基金supported by National Natural Science Foundation of China,30700151Youth Investigator Fund from UESTC,Y02018023601062
文摘Emodin [1,3,8-Trihydroxy-6-methylanthraquinone] has been reported to exhibit vascular anti-inflammatory properties.However,the relevant anti-inflammatory mechanisms are not well understood.The present study was design to explore the molecular target(s) of emodin
基金financially supported by the National Natural Science Foundation of China(31571722 and 31971984)the Funds for Creative Research Groups of China(31621005)the Genetically Modified Organisms Breeding Major Project of China(No.2018ZX0800921B)。
文摘Background:Cotton fiber is a single-celled seed trichome that originates from the ovule epidermis.It is an excellent model for studying cell elongation.Along with the elongation of cotton fiber cell,the plasma membrane is also extremely expanded.Despite progress in understanding cotton fiber cell elongation,knowledge regarding the relationship of plasma membrane in cotton fiber cell development remains elusive.Methods:The plasma membrane of cotton fiber cells was marked with a low toxic fluorescent dye,di-4-ANEPPDHQ,at different stages of development.Fluorescence images were obtained using a confocal laser scanning microscopy.Subsequently,we investigated the relationship between lipid raft activity and cotton fiber development by calculating generalized polarization(GP values)and dual-channel ratio imaging.Results:We demonstrated that the optimum dyeing conditions were treatment with 3μmol·L-1 di-4-ANEPPDHQ for 5 min at room temperature,and the optimal fluorescence images were obtained with 488 nm excitation and500–580 nm and 620–720 nm dual channel emission.First,we examined lipid raft organization in the course of fiber development.The GP values were high in the fiber elongation stage(5–10 DPA,days past anthesis)and relatively low in the initial(0 DPA),secondary cell wall synthesis(20 DPA),and stable synthesis(30 DPA)stages.The GP value peaked in the 10 DPA fiber,and the value in 30 DPA fiber was the lowest.Furthermore,we examined the differences in lipid raft activity in fiber cells between the short fiber cotton mutant,Li-1,and its wild-type.The GP values of the Li-1 mutant fiber were lower than those of the wild type fiber at the elongation stage,and the GP values of 10 DPA fibers were lower than those of 5 DPA fibers in the Li-1 mutant.Conclusions:We established a system for examining membrane lipid raft activity in cotton fiber cells.We verified that lipid raft activity exhibited a low-high-low change regularity during the development of cotton fiber cell,and the pattern was disrupted in the short lint fiber Li-1 mutant,suggesting that membrane lipid order and lipid raft activity are closely linked to fiber cell development.
基金supported by a grant from Projects of High-tech Industrialization of Guangdong Province of China,No.2011B010500004a grant from National Financial Major Project of China
文摘Amyloid-beta peptide is the main component of amyloid plaques,which are found in Alzheimer’s disease.The generation and deposition of amyloid-beta is one of the crucial factors for the onset and progression of Alzheimer’s disease.Lipid rafts are glycolipid-rich liquid domains of the plasma membrane,where certain types of protein tend to aggregate and intercalate.Lipid rafts are involved in the generation of amyloid-beta oligomers and the formation of amyloid-beta peptides.In this paper,we review the mechanism by which lipid rafts disturb the aberrant degradative autophagic-lysosomal pathway of amyloid-beta,which plays an important role in the pathological process of Alzheimer’s disease.Moreover,we describe this mechanism from the view of the Two-system Theory of fasciology and thus,suggest that lipid rafts may be a new target of Alzheimer’s disease treatment.
基金supported by aBBSRC grant (LAK, RDP)a BBSRC-funded PhDstudentship (FJH)
文摘GP64 is the major envelope glycoprotein associated with the budded virus (BV) of Autographa californica nucleopolyhedrovirus (AcMNPV) and is essential for attachment and budding of BV particles. Confocal microscopy and flotation assays established the presence of lipid raft domains within the plasma membranes of AcMNPV-infected Sf9 cells and suggested the association of GP64 with lipid rafts during infection. GP64 and filamentous actin (F-actin) were found to co-localise at the cell cortex at 24 and 48 hpi and an additional restructuring of F-actin during infection was visualised, resulting in a strongly polarised distribution of both F-actin and GP64 at the cell cortex. Depletion of F-actin, achieved by treatment of Sf9 cells with latrunculin B (LB), resulted in the redistribution of GP64 with significant cytoplasmic aggregation and reduced presence at the plasma membrane. Treatment with LB also resulted in reduced production of BV in Sf9 cells. Analysis of virus gene transcription confirmed this reduction was not due to decreased trafficking of nucleocapsids to the nucleus or to decreased production of infectious progeny nucleocapsids. Reduced BV production due to a lack of GP64 at the plasma membrane of AcMNPV-infected Sf9 cells treated with LB, suggests a key role for F-actin in the egress of BV.
基金Supported by the National Natural Science Foundation of China (No. 30340420442,30330160)the National Basic Research Program of China (No.2004 CB720005)
文摘Lipid rafts are cholesterol-enriched microdomains and implicated in many essential physiological ac-tivities such as the neurotransmitter release.Many studies have been carried out on the function of rafts inthe plasma membranes,whereas little is known about the information of such microdomains in subcellularcompartments especially synaptic vesicles(SVs).In the well-studied plasma membranes,several proteinshave been recognized as raft markers,which are used to label or trace rafts.But the raft marker proteinon SVs has not been identified yet.Although some SV proteins,including VAMP and CPE,have beenfound in raft fractions,they cannot be used as markers due to their low abundance in rafts.In this work,we designed several chimera proteins and tested their characteristics for using as SV raft makers.First,we detected whether they located in SVs,and then the chimeras exhibiting the better localization in SVswere further examined for their enrichment in raft using detergent treatment and gradient density floatationanalysis.Our results indicate that one of the chimeric proteins is primarily located in SVs and distributedin raft microdomains,which strongly suggests that it could be served as a raft marker for SVs.
基金fiancial support from the National Natural Science Foundation of China(NSFC No.61475196)。
文摘Cholesterol,as a common lipid on mammalian cell membranes,plays an important role in the formation of lipid rafts.Recent experiments suggest that the strength of cholesterol's regulation on lipid rafts can be affected by the length of the unsaturated phospholipid acyl chain on the membrane.In order to understand this observation,a simplified toy model containing three different molecules is proposed in this paper,where the tail length of phospholipids is considered.This model shows the regulation of membrane cholesterol on the phase separation of the lipid mixture and the formation of nano-domains,and also suggests that the configuration entropy of phospholipid tails is an essential factor.
基金This work was supported by the national key project for infectious dis-ease control and prevention(Grant no 2018ZX10711-001)the Strate-gic Priority Research Program of Chinese Academy of Sciences(No.XDB29050201).
文摘Ebola virus(EBOV)is one of the most pathogenic viruses in humans which can cause a lethal hemorrhagic fever.Understanding the cellular entry mechanisms of EBOV can promote the development of new therapeutic strategies to control virus replication and spread.It has been known that EBOV virions bind to factors expressed at the host cell surface.Subsequently,the virions are internalized by a macropinocytosis-like process,followed by being trafficked through early and late endosomes.Recent researches indicate that the entry of EBOV into cells requires integrated and functional lipid rafts.Whilst lipid rafts have been hypothesized to play a role in virus entry,there is a current lack of supporting data.One major technical hurdle is the lack of effective approaches for observing viral entry.To provide evidence on the involvement of lipid rafts in the entry process of EBOV,we generated the fluorescently labeled Ebola virus like particles(VLPs),and utilized single-particle tracking(SPT)to visualize the entry of fluorescent Ebola VLPs in live cells and the interaction of Ebola VLPs with lipid rafts.In this study,we demonstrate the compartmentalization of Ebola VLPs in lipid rafts during entry process,and inform the essential function of lipid rafts for the entry of Ebola virus.As such,our study provides evidence to show that the raft integrity is critical for Ebola virus pathogenesis and that lipid rafts can serve as potential targets for the development of novel therapeutic strategies.
文摘The first appearance of lipid rafts,or lipid rafts-like structure,was occasionally observed by cryo-electronic microscopy in 1980s as cavity,such as caveolae. However,the fully understanding of lipid raft was attributed by the studies of T cell activation,virus entry/budding,and other membrane events. During the interaction of T cell and antigen presenting cell,a highly organized structure is formed at the interface of the two cells,where cholesterol and sphingolipids are enriched,and form a liquid ordered phase that facilitates the signaling proteins on and off. Lipid rafts are also involved in virus entry and assembly. In this review,we will discuss cholesterol-sphingolipid floating microdomain,the lipid raft as a unique compartment of the plasma membrane,with biological functions that ensure correct intracellular traffic of proteins and lipids,such as protein-protein interactions by concentrating certain proteins in these microdomains,while excluding others. We also discuss the disruption of lipid rafts is related to different diseases and aging,and we especially exploit the lipid rafts as pharmaceutical targets for anti-virus and anti-inflammation,particularly a new approach to control HIV infection for AIDS prevention and protection by inhibition or disruption of lipid rafts.
文摘Recent studies have shown that polyunsaturated fatty acids (PUFA) regulated the func-tions of membrane receptors in T cells and suppressed T cell -mediated immune responses. But the molecular mechanisms of immune regulation are not yet elucidated. Lipid rafts are plasma membrane microdomains, in which many receptors localized. The purpose of this study was to investigate the effect of DHA on IL-2R signaling pathway in lipid rafts. We isolated lipid rafts by discontinuous sucrose density gradient ultracentrifugation, and found that DHA could change the composition of lipid rafts and alter the distribution of key molecules of IL-2R signaling pathway, which transferred from lipid rafts to detergent-soluble membrane fractions. These results revealed that DHA treatment increased the proportion of polyunsaturated fatty acids especially n?3 polyunsaturated fatty acids in lipid rafts and changed the lipid environment of membrane microdomains in T cells. Compared with controls, DHA changed the localization of IL-2R, STAT5a and STAT5b in lipid rafts and suppressed the expression of JAK1, JAK3 and tyrosine phosphotyrosine in soluble membrane fractions. Summarily, this study con-cluded the effects of DHA on IL-2R signaling pathway in lipid rafts and explained the regulation of PUFAs in T cell-mediated immune responses.
基金Supported by the National Natural Science Foundation of China (Grant Nos. 30670501 and 30628007)the National Basic Research Program of China (Grant No. 2004 CB720005)
文摘In this paper we report that the C2 domain of synaptotagmin I (syt I) could associate with lipid rafts of plasma membrane. We demonstrate that phosphatidylinositol 4,5-bisphosphate (PIP2) in the target membrane and Ca2+ are the key factors to enhance the raft association of the C2 domain. We also found that the raft association of the C2 domain could be fulfilled by either C2A or C2B alone, suggesting that their raft association might be complementary. Finally, we indicate that destroying lipid rafts or blocking syt I-raft association could significantly reduce the Ca2+-driven release of glutamates. Our data indicate that the raft association of the C2 domain might play an important role in the regulated exocytosis.
基金Supported by the National Key Basic Research and Development (973) Program of China (No. 2004CB720005)
文摘For a long time, lipid rafts have been thought to participate in regulating neurotransmitter release. However,the existence of lipid rafts on synaptic vesicles (SVs) and the mechanism by which exocytosis-relative proteins distribute on this structure have not been fully investigated. There is also much controver-sial data concerning rafts on SVs and synaptic vesicle proteins which makes the results difficult to interpret. This study systematically analyzed the existence and properties of lipid rafts on purified SVs by sucrose density gradient centrifugation, cholesterol depletion, and temperature variation. The data reveals that typi-cal lipid rafts on SVs are both cholesterol dependent and temperature sensitive. Previous confusing results may have been caused by improper treatment or side effects of particular reagent. We also screened the lateral distribution of major exocytosis-related SV proteins and found that only the synaptobrevin (syb) and synaptotagmin (syt) produce detectable association with lipid rafts in 1% Triton X-100.
基金Supported by The Ministry of Education,Culture,Sports,Science and Technology of Japan through grant-in-aid 26461103(to Amiya E)
文摘Reactive oxygen species(ROS) and oxidative stress are closely associated with the development of atherosclerosis,and the most important regulator of ROS production in endothelial cells is NADPH oxidase.Activation of NADPH oxidase requires the assembly of multiple subunits into lipid rafts,which include specific lipid components,including free cholesterol and specific proteins.Disorders of lipid metabolism such as hyperlipidemia affect the cellular lipid components included in rafts,resulting in modification of cellular reactions that produce ROS.In the similar manner,several pathways associating ROS production are affected by the presence of lipid disorder through raft compartments.In this manuscript,we review the pathophysiological implications of hyperlipidemia and lipid rafts in the production of ROS.
基金This work was supported by the National Natural Science Foundation of China(Grant No.81772629 and 81974374).
文摘Carbohydrates,lipids,and proteins are the three major nutrients required by the human body.The lipids,comprising triglycerides,phospholipids,and sterols,provide energy and essential fatty acids for the body,and are required for the growth and maintenance of human cells and tissues.A variety of lipid molecules and their intermediates are involved in cell signaling and inflammation,and have been reported to promote tumor transformation and progression.Fatty acid biosynthetic enzymes are also involved in the lipid metabolism of tumors.Dyslipidemia is closely related to many solid tumors,and may both play a role in both tumorigenesis and be a consequence of tumor development.Therefore,abnormal lipid metabolism is strongly associated with tumor transformation and progression.This review discusses the signaling pathways,related genes,enzymes,and inflammatory cell factors involved in tumor lipid metabolism,as well as the roles of dyslipidemia in tumor transformation and progression.We believe the information provided will serve as valuable reference highlighting molecules that can be targeted to improve the treatment of tumors.
基金Project supported by the Hundred-Talent Program of the Chinese Academy of Sciences(FY)the National Science Foundation of USA via Grant DMR-1106014(RLBS,JVS)
文摘We investigate how an externally imposed curvature influences lipid segregation on two-phase-coexistent membranes.We show that the bending-modulus contrast of the two phases and the curvature act together to yield a reduced effective line tension.On largely curved membranes,a state of multiple domains(or rafts) forms due to a mechanism analogous to that causing magnetic-vortex formation in type-II superconductors.We determine the criterion for such a multi-domain state to occur;we then calculate respectively the size of the domains formed on cylindrically and spherically curved membranes.