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Endocytic regulation of TGF-β signaling 被引量:16
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作者 Ye-Guang Chen 《Cell Research》 SCIE CAS CSCD 2009年第1期58-70,共13页
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
关键词 TGF-Β ENDOCYTOSIS CLATHRIN lipid rafts endosome
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网织红细胞铁摄取机制的研究进展 被引量:12
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作者 钱忠明 蒲咏梅 邓柏礼 《生物化学与生物物理进展》 SCIE CAS CSCD 北大核心 1997年第1期8-13,共6页
从细胞及分子水平重点讨论了有关网织红细胞铁代谢的两个问题 .a 网织红细胞如何摄取载铁蛋白结合铁 ?分七个主要步骤总结了这一摄取过程的研究新进展 .b 在内吞小体内 ,铁从载铁蛋白释放后如何穿越内吞小体膜进入细胞质 ?论述了有关的... 从细胞及分子水平重点讨论了有关网织红细胞铁代谢的两个问题 .a 网织红细胞如何摄取载铁蛋白结合铁 ?分七个主要步骤总结了这一摄取过程的研究新进展 .b 在内吞小体内 ,铁从载铁蛋白释放后如何穿越内吞小体膜进入细胞质 ?论述了有关的机制 ,包括铁通道假说 ,铁载体 ,H+ ATP酶介导的铁转位 ,自由基和过氧化物的作用 . 展开更多
关键词 网织红细胞 摄取
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Stay in touch with the endoplasmic reticulum 被引量:2
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作者 Sha Sun Gan Zhao +14 位作者 Mingkang Jia Qing Jiang Shulin Li Haibin Wang Wenjing Li Yunyun Wang Xin Bian Yan G.Zhao Xun Huang Ge Yang Huaqing Cai Jose C.Pastor-Pareja Liang Ge Chuanmao Zhang Junjie Hu 《Science China(Life Sciences)》 SCIE CAS CSCD 2024年第2期230-257,共28页
The endoplasmic reticulum(ER),which is composed of a continuous network of tubules and sheets,forms the most widely distributed membrane system in eukaryotic cells.As a result,it engages a variety of organelles by est... The endoplasmic reticulum(ER),which is composed of a continuous network of tubules and sheets,forms the most widely distributed membrane system in eukaryotic cells.As a result,it engages a variety of organelles by establishing membrane contact sites(MCSs).These contacts regulate organelle positioning and remodeling,including fusion and fission,facilitate precise lipid exchange,and couple vital signaling events.Here,we systematically review recent advances and converging themes on ER-involved organellar contact.The molecular basis,cellular influence,and potential physiological functions for ER/nuclear envelope contacts with mitochondria,Golgi,endosomes,lysosomes,lipid droplets,autophagosomes,and plasma membrane are summarized. 展开更多
关键词 endoplasmic reticulum nuclear envelope MITOCHONDRIA Golgi apparatus endosome LYSOSOME lipid droplets AUTOPHAGOSOME plasma membrane membrane contact site
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The RING E3 ligase CLG1 targets GS3 for degradation via the endosome pathway to determine grain size in rice 被引量:7
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作者 Wensi Yang Kun Wu +10 位作者 Bo Wang Huanhuan Liu Siyi Guo Xiaoyu Guo Wei Luo Shengyuan Sun Yidan Ouyang Xiangdong Fu Kang Chong Qifa Zhang Yunyuan Xu 《Molecular Plant》 SCIE CAS CSCD 2021年第10期1699-1713,共15页
G-protein signaling and ubiquitin-dependent degradation are both involved in grain development in rice,but how these pathways are coordinated in regulating this process is unknown.Here,we show that Chang Li Geng 1(CLG... G-protein signaling and ubiquitin-dependent degradation are both involved in grain development in rice,but how these pathways are coordinated in regulating this process is unknown.Here,we show that Chang Li Geng 1(CLG1),which encodes an E3 ligase,regulates grain size by targeting the Gγprotein GS3,a negative regulator of grain length,for degradation.Overexpression of CLG1 led to increased grain length,while overexpression of mutated CLG1 with changes in three conserved amino acids decreased grain length.We found that CLG1 physically interacts with and ubiquitinats GS3which is subsequently degraded through the endosome degradation pathway,leading to increased grain size.Furthermore,we identified a critical SNP in the exon 3 of CLG1 that is significantly associated with grain size variation in a core collection of cultivated rice.This SNP results in an amino acid substitution from Arg to Ser at position 163 of CLG1 that enhances the E3 ligase activity of CLG1 and thus increases rice grain size.Both the expression level of CLG1 and the SNP CLG1163S may be useful variations for manipulating grain size in rice. 展开更多
关键词 grain size CLG1 GS3 E3 ligase endosome
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ESCRT系统:一个多功能的蛋白转运及膜剪切机器 被引量:7
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作者 黄欢 李万杰 杨冬 《中国生物化学与分子生物学报》 CAS CSCD 北大核心 2013年第2期99-109,共11页
转运必需内体分选复合物(endosomal sorting complex required for transport,ESCRT)系统是真核细胞中完成内体(endosome)膜内陷以形成多囊泡体(multi-vesicular body,MVB)的分子机器.其主要功能是促进被泛素(ubiquitin)标记的膜蛋白的... 转运必需内体分选复合物(endosomal sorting complex required for transport,ESCRT)系统是真核细胞中完成内体(endosome)膜内陷以形成多囊泡体(multi-vesicular body,MVB)的分子机器.其主要功能是促进被泛素(ubiquitin)标记的膜蛋白的降解,还与细胞分裂、病毒出芽、细胞自噬以及真菌pH感知相关.ESCRT系统包括ESCRT-0,-Ⅰ,-Ⅱ,-Ⅲ和Vps4-Vta1共5个蛋白-蛋白复合物.晶体学研究已经解析了大部分复合物的结构.其促使膜内陷的分子机理一般认为分3步.首先是ESCRT-Ⅰ和-Ⅱ在内体膜上结合并促使内体膜内陷形成初始芽体.之后,ESCRT-Ⅲ在芽体颈部聚合并导致芽体的剪切,从而将内腔囊泡(intralumenal vesicles,ILVs)释放到内体腔内,形成MVB.最后,Vps4/Vta1复合物则以水解ATP提供能量将聚合的ESCRT-Ⅲ解聚以循环使用,完成更多的出芽过程.本文将对ESCRT系统的结构、出芽机理和生物功能几方面做一个综述. 展开更多
关键词 转运必需内体分选复合物 膜转运 内体 多囊泡体
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A multi-functional nanoplatform for efficacy tumor theranostic applications 被引量:4
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作者 Jinjin Shi Hongling Zhang +2 位作者 Zhaoyang Chen Lihua Xu Zhenzhong Zhang 《Asian Journal of Pharmaceutical Sciences》 SCIE CAS 2017年第3期235-249,共15页
Nanomaterials with multiple functions have become more and more popular in the domain of cancer research. MoS2 has a great potential in photothermal therapy, X-ray/CT imaging and drug delivery. In this study, a water ... Nanomaterials with multiple functions have become more and more popular in the domain of cancer research. MoS2 has a great potential in photothermal therapy, X-ray/CT imaging and drug delivery. In this study, a water soluble MoS2 nanosystem(MoS2-PEG) was synthesized and explored in drug delivery, photothermal therapy(PTT) and X-ray imaging.Doxorubicin(DOX) was loaded onto MoS2-PEG with a high drug loading efficiency(~69%)and obtained a multifunctional drug delivery system(MoS2-PEG/DOX). As the drug delivery, MoS2-PEG/DOX could efficiently cross the cell membranes, and escape from the endosome via NIR light irradiation, lead to more apoptosis in MCF-7 cells, and afford higher antitumor efficacy without obvious toxic effects to normal organs owing to its prolonged blood circulation and 11.6-fold higher DTX uptake of tumor than DOX. Besides, MoS2-PEG/DOX not only served as a drug delivery system, but also as a powerful PTT agent for thermal ablation of tumor and a strong X-ray contrast agent for tumor diagnosis. In the in vitro and in vivo studies, MoS2-PEG/DOX exhibited excellent tumor-targeting efficacy, outstanding synergistic anti-cancer effect of photothermal and chemotherapy and X-ray imaging property,demonstrating that MoS2-PEG/DOX had a great potential for simultaneous diagnosis and photothermal-chemotherapy in cancer treatment. 展开更多
关键词 MULTIFUNCTIONAL drug delivery endosome ESCAPE TUMOR-TARGETING BIO-IMAGING THERANOSTIC
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M6PR interacts with the HA2 subunit of influenza A virus to facilitate the fusion of viral and endosomal membranes
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作者 Yuzhen Hu Li Jiang +10 位作者 Guangwen Wang Yangming Song Zhibo Shan Xuyuan Wang Guohua Deng Jianzhong Shi Guobin Tian Xianying Zeng Liling Liu Hualan Chen Chengjun Li 《Science China(Life Sciences)》 SCIE CAS CSCD 2024年第3期579-595,共17页
Influenza A virus(IAV) commandeers numerous host cellular factors for successful replication. However, very few host factors have been revealed to be involved in the fusion of viral envelope and late endosomal membran... Influenza A virus(IAV) commandeers numerous host cellular factors for successful replication. However, very few host factors have been revealed to be involved in the fusion of viral envelope and late endosomal membranes. In this study, we identified cation-dependent mannose-6-phosphate receptor(M6PR) as a crucial host factor for the replication of IAV. We found that siRNA knockdown of M6PR expression significantly reduced the growth titers of different subtypes of IAV, and that the inhibitory effect of M6PR siRNA treatment on IAV growth was overcome by the complement of exogenously expressed M6PR. When A549 cells were treated with siRNA targeting M6PR,the nuclear accumulation of viral nucleoprotein(NP) was dramatically inhibited at early timepoints post-infection, indicating that M6PR engages in the early stage of the IAV replication cycle. By investigating the role of M6PR in the individual entry and post-entry steps of IAV replication, we found that the downregulation of M6PR expression had no effect on attachment, internalization, early endosome trafficking,or late endosome acidification. However, we found that M6PR expression was critical for the fusion of viral envelope and late endosomal membranes. Of note, M6PR interacted with the hemagglutinin(HA) protein of IAV, and further studies showed that the lumenal domain of M6PR and the ectodomain of HA2 mediated the interaction and directly promoted the fusion of the viral and late endosomal membranes,thereby facilitating IAV replication. Together, our findings highlight the importance of the M6PR–HA interaction in the fusion of viral and late endosomal membranes during IAV replication. 展开更多
关键词 influenza A virus M6PR HA membrane fusion late endosome
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KIF5B-mediated internalization of FMDV promotes virus infection
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作者 Wei Zhang Fan Yang +9 位作者 Yang Yang Weijun Cao Wenhua Shao Jiali Wang Mengyao Huang Zhitong Chen Xiaoyi Zhao Weiwei Li Zixiang Zhu Haixue Zheng 《Virologica Sinica》 SCIE CAS CSCD 2024年第3期378-389,共12页
Foot-and-mouth disease(FMD)is a highly contagious and economically important disease,which is caused by the FMD virus(FMDV).Although the cell receptor for FMDV has been identified,the specific mechanism of FMDV intern... Foot-and-mouth disease(FMD)is a highly contagious and economically important disease,which is caused by the FMD virus(FMDV).Although the cell receptor for FMDV has been identified,the specific mechanism of FMDV internalization after infection remains unknown.In this study,we found that kinesin family member 5B(KIF5B)plays a vital role during FMDV internalization.Moreover,we confirmed the interaction between KIF5B and FMDV structural protein VP1 by co-immunoprecipitation(Co-IP)and co-localization in FMDV-infected cells.In particular,the stalk[amino acids(aa)413–678]domain of KIF5B was indispensable for KIF5B-VP1 interaction.Moreover,overexpression of KIF5B dramatically enhanced FMDV replication;consistently,knockdown or knockout of KIF5B suppressed FMDV replication.Furthermore,we also demonstrated that KIF5B promotes the internalization of FMDV via regulating clathrin uncoating.KIF5B also promotes the transmission of viral particles to early and late endosomes during the early stages of infection.In conclusion,our results demonstrate that KIF5B promotes the internalization of FMDV via regulating clathrin uncoating and intracellular transport.This study may provide a new therapeutic target for developing FMDV antiviral drugs. 展开更多
关键词 FMDV VP1 protein KIF5B endosome CLATHRIN
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鸡恒定链协助抗原肽结合MHCⅡ类分子并进入细胞内吞体 被引量:5
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作者 陈芳芳 张旭 +2 位作者 谭红黎 桂亚萍 余为一 《畜牧兽医学报》 CAS CSCD 北大核心 2019年第2期398-405,共8页
为探明鸡恒定链(invariant chain,Ii)的胞质区/跨膜区[Ii(Cyt/Tra)]作为载体是否可携带抗原肽在细胞内结合MHCⅡ类分子和进入转运途径的细胞器(内吞体),构建4个基因目的片段[Ii、Ii(Cyt/Tra)、F2(新城疫病毒F蛋白片段)和Ii(Cyt/Tra)/F2]... 为探明鸡恒定链(invariant chain,Ii)的胞质区/跨膜区[Ii(Cyt/Tra)]作为载体是否可携带抗原肽在细胞内结合MHCⅡ类分子和进入转运途径的细胞器(内吞体),构建4个基因目的片段[Ii、Ii(Cyt/Tra)、F2(新城疫病毒F蛋白片段)和Ii(Cyt/Tra)/F2],分别将它们插入原核表达载体pET-32a和真核表达载体pmCherry-C1/N1中,构建8个重组质粒,再转入工程菌(E.coli)和人肾细胞系(293T),并应用拉下法(pull-down)检测目的蛋白与MHCⅡβ的结合,应用激光共聚焦确定它们在真核细胞与MHCⅡβ的共定位以及在内吞体的定位。结果表明,构建的重组质粒均能相应地原核或真核表达相应目的蛋白;Ii、Ii(Cyt/Tra)和Ii(Cyt/Tra)/F2不仅能够与MHCⅡβ结合,还能进入细胞内吞体;但是F2既不能与MHCⅡβ结合,也不能进入内吞体。Ii活性片段Cyt/Tra不仅本身具有结合MHCⅡβ的作用,而且还可以携带抗原肽与之结合并一起转入细胞内吞体而进入抗原递呈途径。该结果为进一步研究Ii载体转运抗原提供了理论依据。 展开更多
关键词 II 活性片段 免疫载体 内吞体 抗原递呈
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Lipid carriers for mRNA delivery 被引量:1
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作者 Wanting Zhang Yuxin Jiang +4 位作者 Yonglong He Hamza Boucetta Jun Wu Zhongjian Chen Wei He 《Acta Pharmaceutica Sinica B》 SCIE CAS CSCD 2023年第10期4105-4126,共22页
Messenger RNA(mRNA)is the template for protein biosynthesis and is emerging as an essential active molecule to combat various diseases,including viral infection and cancer.Especially,mRNA-based vaccines,as a new type ... Messenger RNA(mRNA)is the template for protein biosynthesis and is emerging as an essential active molecule to combat various diseases,including viral infection and cancer.Especially,mRNA-based vaccines,as a new type of vaccine,have played a leading role in fighting against the current global pandemic of COVID-19.However,the inherent drawbacks,including large size,negative charge,and instability,hinder its use as a therapeutic agent.Lipid carriers are distinguishable and promising vehicles for mRNA delivery,owning the capacity to encapsulate and deliver negatively charged drugs to the targeted tissues and release cargoes at the desired time.Here,we first summarized the structure and properties of different lipid carriers,such as liposomes,liposome-like nanoparticles,solid lipid nanoparticles,lipid-polymer hybrid nanoparticles,nanoemulsions,exosomes and lipoprotein particles,and their applications in delivering mRNA.Then,the development of lipid-based formulations as vaccine delivery systems was discussed and highlighted.Recent advancements in the mRNA vaccine of COVID-19 were emphasized.Finally,we described our future vision and perspectives in this field. 展开更多
关键词 MRNA Lipid carriers Drug delivery endosome escape NANOPARTICLES Encapsulation efficiency VACCINE COVID-19
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Converging links between adult-onset neurodegenerative Alzheimer’s disease and early life neurodegenerative neuronal ceroid lipofuscinosis? 被引量:1
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作者 Marcel Klein Guido Hermey 《Neural Regeneration Research》 SCIE CAS CSCD 2023年第7期1463-1471,共9页
Evidence from genetics and from analyzing cellular and animal models have converged to suggest links between neurodegenerative disorders of early and late life.Here,we summarize emerging links between the most common ... Evidence from genetics and from analyzing cellular and animal models have converged to suggest links between neurodegenerative disorders of early and late life.Here,we summarize emerging links between the most common late life neurodegenerative disease,Alzheimer’s disease,and the most common early life neurodegenerative diseases,neuronal ceroid lipofuscinoses.Genetic studies reported an overlap of clinically diagnosed Alzheimer’s disease and mutations in genes known to cause neuronal ceroid lipofuscinoses.Accumulating data strongly suggest dysfunction of intracellular trafficking mechanisms and the autophagy-endolysosome system in both types of neurodegenerative disorders.This suggests shared cytopathological processes underlying these different types of neurodegenerative diseases.A better understanding of the common mechanisms underlying the different diseases is important as this might lead to the identification of novel targets for therapeutic concepts,the transfer of therapeutic strategies from one disease to the other and therapeutic approaches tailored to patients with specific mutations.Here,we review dysfunctions of the endolysosomal autophagy pathway in Alzheimer’s disease and neuronal ceroid lipofuscinoses and summarize emerging etiologic and genetic overlaps. 展开更多
关键词 Alzheimer’s disease autophagy Batten disease CLN3 disease dementia endosome LYSOSOME neurodegeneration neuronal ceroid lipofuscinosis PRESENILIN
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透明质酸聚合物胶束的制备及其内涵体的pH敏感性 被引量:5
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作者 刘艳华 周成铭 杨彤 《功能高分子学报》 CAS CSCD 北大核心 2018年第3期255-260,272,共7页
首先以脱氧胆酸(DOCA)和三苯甲基组氨酸甲酯盐酸盐(H-His(Trt)-OMe·HCl)为反应物,经催化剂缩合制得DOCA-His(Trt)中间体。然后将透明质酸(HA)经N-羟基琥珀酰亚胺(NHS)和1-乙基-(3-二甲基氨基丙基)碳酰二亚胺盐酸盐(EDC·HCl)... 首先以脱氧胆酸(DOCA)和三苯甲基组氨酸甲酯盐酸盐(H-His(Trt)-OMe·HCl)为反应物,经催化剂缩合制得DOCA-His(Trt)中间体。然后将透明质酸(HA)经N-羟基琥珀酰亚胺(NHS)和1-乙基-(3-二甲基氨基丙基)碳酰二亚胺盐酸盐(EDC·HCl)活化形成活性酯。最后将活性酯接枝DOCA-His(Trt)中间体,制得HA-DOCA-His(Trt)聚合物,脱Trt保护,制得HADOCA-His聚合物。采用FT-IR鉴定HA-DOCA-His的化学结构,并评价其溶血性和pH敏感性,通过超声法制备载紫杉醇的HA-DOCA-His胶束,并以透析法考察其体外释药行为。采用MTT法考察胶束的细胞毒性。结果表明,HA-DOCA-His溶血性与聚氧乙烯蓖麻油(Cremophor EL)相当,远远低于Tween 80;载紫杉醇的HA-DCA-His胶束在模拟内涵体环境中具有触发释药行为;相比于紫杉醇溶液,HA-DOCA-His载药胶束在模拟内涵体pH环境下表现出高效抑制MCF-7肿瘤细胞的增殖作用;HA-DOCA-His胶束可作为CD44受体和内涵体pH敏感的多靶向胶束载药系统,用于难溶性抗肿瘤药物的肿瘤靶向递药和胞内靶向释药。 展开更多
关键词 HA-DOCA-His 聚合物胶束 内涵体 PH敏感性 CD44受体靶向 紫杉醇
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Adenosine Diphosphate Ribosylation Factor-GTPase-Activating Protein Stimulates the Transport of AUX1 Endosome,Which Relies on Actin Cytoskeletal Organization in Rice Root Development 被引量:2
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作者 Cheng Du Yunyuan Xu +1 位作者 Yingdian Wang Kang Chong 《Journal of Integrative Plant Biology》 SCIE CAS CSCD 2011年第9期698-709,共12页
Polar auxin transport,which depends on polarized subcellular distribution of AUXIN RESISTANT 1/LIKE AUX1(AUX1/LAX) influx carriers and PIN-FORMED(PIN) efflux carriers,mediates various processes of plant growth and... Polar auxin transport,which depends on polarized subcellular distribution of AUXIN RESISTANT 1/LIKE AUX1(AUX1/LAX) influx carriers and PIN-FORMED(PIN) efflux carriers,mediates various processes of plant growth and development.Endosomal recycling of PIN1 is mediated by an adenosine diphosphate(ADP)ribosylation factor(ARF)-GTPase exchange factor protein,GNOM.However,the mediation of auxin influx carrier recycling is poorly understood.Here,we report that overexpression of OsAGAP,an ARF-GTPase-activating protein in rice,stimulates vesicle transport from the plasma membrane to the Golgi apparatus in protoplasts and transgenic plants and induces the accumulation of early endosomes and AUX1.AUX1 endosomes could partially colocalize with FM4-64 labeled early endosome after actin disruption.Furthermore,OsAGAP is involved in actin cytoskeletal organization,and its overexpression tends to reduce the thickness and bundling of actin filaments.Fluorescence recovery after photobleaching analysis revealed exocytosis of the AUX1 recycling endosome was not affected in the OsAGAP overexpression cells,and was only slightly promoted when the actin filaments were completely disrupted by Lat B.Thus,we propose that AUX1 accumulation in the OsAGAP overexpression and actin disrupted cells may be due to the fact that endocytosis of the auxin influx carrier AUX1 early endosome was greatly promoted by actin cytoskeleton disruption. 展开更多
关键词 ACTIN adenosine diphosphate ribosylation factor-GTPase-activating protein AUX1 endosome polar auxin transport.
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Orange-derived extracellular vesicles nanodrugs for efficient treatment of ovarian cancer assisted by transcytosis effect
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作者 Feng Long Yao Pan +9 位作者 Jinheng Li Suinan Sha Xiubo Shi Haoyan Guo Chuanqing Huang Qian Xiao Chao Fan Xingmei Zhang Jun-Bing Fan Ying Wang 《Acta Pharmaceutica Sinica B》 SCIE CAS CSCD 2023年第12期5121-5134,共14页
Extracellular vesicles(EVs)have recently received much attention about the application of drug carriers due to their desirable properties such as nano-size,biocompatibility,and high stability.Herein,we demonstrate ora... Extracellular vesicles(EVs)have recently received much attention about the application of drug carriers due to their desirable properties such as nano-size,biocompatibility,and high stability.Herein,we demonstrate orange-derived extracellular vesicles(OEV)nanodrugs(DN@OEV)by modifying cRGD-targeted doxorubicin(DOX)nanoparticles(DN)onto the surface of OEV,enabling significantly enhancing tumor accumulation and penetration,thereby efficiently inhibiting the growth of ovarian cancer.The obtained DN@OEV enabled to inducement of greater transcytosis capability in ovarian cancer cells,which presented the average above 10-fold transcytosis effect compared with individual DN.It was found that DN@OEV could trigger receptor-mediated endocytosis to promote early endosome/recycling endosomes pathway for exocytosis and simultaneously reduce degradation in the early endosomes-late endosomes-lysosome pathway,thereby inducing the enhanced transcytosis.In particular,the zombie mouse model bearing orthotopic ovarian cancer further validated DN@OEV presented high accumulation and penetration in tumor tissue by the transcytosis process.Our study indicated the strategy in enhancing transcytosis has significant implications for improving the therapeutic efficacy of thedrugdelivery system. 展开更多
关键词 Extracellular vesicles TRANSCYTOSIS Cancer treatment Drug delivery system Targeted modification Receptor-mediated endocytosis Intracellular trafficking Recycling endosome
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猪瘟病毒通过网格蛋白介导的内吞途径入侵ST细胞 被引量:4
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作者 梁武龙 方佳 +4 位作者 林鸷 郑敏萍 鲍长磊 王涛 张彦明 《畜牧兽医学报》 CAS CSCD 北大核心 2017年第1期140-149,共10页
病毒入侵易感细胞是病毒建立感染的必要过程,猪瘟病毒如何入侵易感细胞尚未明确。笔者对猪瘟病毒入侵细胞与网格蛋白介导的内吞途径的关系进行了初步研究。通过利用抑制剂氯丙嗪和Dynasore及shRNA技术,对网格蛋白及动力蛋白功能进行抑制... 病毒入侵易感细胞是病毒建立感染的必要过程,猪瘟病毒如何入侵易感细胞尚未明确。笔者对猪瘟病毒入侵细胞与网格蛋白介导的内吞途径的关系进行了初步研究。通过利用抑制剂氯丙嗪和Dynasore及shRNA技术,对网格蛋白及动力蛋白功能进行抑制,干扰网格蛋白介导的内吞途径,发现猪瘟病毒的细胞入侵效率明显下降;通过利用内体酸化抑制剂NH4Cl及shRNA技术下调内体标志蛋白Rab5和Rab7的表达量,发现内体酸化过程受到抑制后猪瘟病毒的感染效率受到了明显抑制。本研究初步证明猪瘟病毒能够利用网格蛋白介导的内吞途径完成对易感细胞的入侵,感染的过程依赖于初级内体和次级内体,为了解猪瘟病毒的感染过程积累了新的数据。 展开更多
关键词 猪瘟病毒 入侵 网格蛋白 内体
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Rab5与Rab7调控N2a细胞内狂犬病病毒的早期感染 被引量:3
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作者 李莹莹 王新宇 +5 位作者 陈云云 Waqas Ahmad 曹国燊 段铭 关振宏 张茂林 《中国兽医学报》 CAS CSCD 北大核心 2016年第5期768-771,共4页
狂犬病病毒(rabies virus,RABV)作为一种高度嗜神经性的病毒,通过网格蛋白介导和pH依赖的内吞途径侵入神经细胞,然后经胞内体途径进行传输。已有研究表明,Rab5和Rab7是介导胞内体分选、成熟及定向运输的关键蛋白,而RABV胞内运输是否也... 狂犬病病毒(rabies virus,RABV)作为一种高度嗜神经性的病毒,通过网格蛋白介导和pH依赖的内吞途径侵入神经细胞,然后经胞内体途径进行传输。已有研究表明,Rab5和Rab7是介导胞内体分选、成熟及定向运输的关键蛋白,而RABV胞内运输是否也受到这两者的调控尚不清楚。本试验通过免疫荧光、Western blot及TCID50等技术,检测了N2a中RABV核蛋白(N)和Rab5与Rab7的胞内共定位及RNAi下调Rab5与Rab7表达时,N蛋白表达水平、病毒滴度等的变化。结果发现,Rab5和Rab7与RABV N蛋白存在共定位;当Rab5和Rab7表达下调,RABV感染初期N蛋白表达显著下降,且病毒TCID50也随之降低。结果表明,RABV感染受Rab5和Rab7调节。为进一步解析狂犬病病毒逆轴浆传输机制提供了新的数据。 展开更多
关键词 Rab5 Rab7 狂犬病病毒 胞内体 早期感染
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AtSYP51/52 Functions Diverge in the Post-Golgi Traffic and Differently Affect Vacuolar Sorting
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作者 Maria De Benedictis Gianluca Bleve +5 位作者 Marianna Faraco Egidio Stigliano Francesco Grieco Gabriella Piro Giuseppe Dalessandro Gian Pietro Di Sansebastiano 《Molecular Plant》 SCIE CAS CSCD 2013年第3期916-930,共15页
Plant sensitive factor attachment protein receptors (SNAREs) encoded by genes of the same sub-family are generally considered as redundant in promoting vesicle-associated membrane fusion events. Nonetheless, the app... Plant sensitive factor attachment protein receptors (SNAREs) encoded by genes of the same sub-family are generally considered as redundant in promoting vesicle-associated membrane fusion events. Nonetheless, the application of innovative experimental approaches highlighted that members of the same gene sub-family often have different functional specificities. In this work, two closely related Qc-SNAREs--the AtSYP51 and the AtSYP52--are compared in their ability to influence different secretory pathways. Their role in the vesicle sorting to the central vacuole has been revised and they were found to have a novel inhibitory function. When transiently overexpressed, the SYP51 and the SYP52 distributed between the TGN and the tonoplast. Our data demonstrate that these SYPs (syntaxin of plants) act as t-SNARE when present on the membrane of TGN/PVC, whereas they behave as inhibitory or interfering SNAREs (i-SNAREs) when they accumulate on the tonoplast. Moreover, the performed functional analysis indicated that the AtSYP51 and the AtSYP52 roles differ in the traffic to the vacuole. The findings are a novel contribution to the functional characterization of plant SNAREs that reveals additional non-fusogenic roles. 展开更多
关键词 endocytosis endosome Golgi i-SNARE plant endomembranes protoplast SNARE TGN TONOPLAST vacuole.
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CONTRIBUTION OF CHOLESTEROL MOIETIES ATTACHED ON MPEG-b-PCL-b-PLL TO THE CELL UPTAKE, ENDOSOMAL ESCAPE AND GENE KNOCKDOWN OF THE MICELLEPLEXES OF siRNA
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作者 Ruo-gu Qi Su-hong Wu +4 位作者 Yu Wang Jie Chen Zhi-gang Xie Yu-bin Huang 景遐斌 《Chinese Journal of Polymer Science》 SCIE CAS CSCD 2013年第6期912-923,共12页
To further enhance the transfection efficiency of a micelleplex system based on monomethoxy poly(ethylene glycol)-block-poly(e-caprolactone)-block-poly(L-lysine) (MPEG-b-PCL-b-PLL), cholesterol (Chol) moieti... To further enhance the transfection efficiency of a micelleplex system based on monomethoxy poly(ethylene glycol)-block-poly(e-caprolactone)-block-poly(L-lysine) (MPEG-b-PCL-b-PLL), cholesterol (Chol) moieties are attached to the e-termini of PLL segments to obtain MPEG-b-PCL-b-PLL/Chol. The structure and morphology of the copolymer are studied by IH-NMR, TEM and DLS (dynamic light scattering). The cytotoxicity, cell uptake, endosomal release and mRNA knockdown are studied by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay, flow cytometry, CLSM (confocal laser scanning microscopy) and RT-PCR (real-time polymerase chain reaction). The results show that compared to their precursor MPEG-b-PCL-b-PLL, the cholesterol-grafted copolymer shows significantly lower toxicity, more rapid cellular endocytosis and endosome escape, and consequently displays enhanced siRNA transfection efficiency even at a lower N/P ratio. These improvements are ascribed to enhanced interaction of the cholesterol moieties with both cellular membrane and endosomal membrane. Moreover, effect of the PLL block length is examined. The final conclusion is that long enough PLL segments and incorporation of proper fraction of cholesterol onto the PLL segments benefit the enhancement of siRNA transfection efficiency. 展开更多
关键词 Amphiphilic copolymer CHOLESTEROL endosome escape Micelleplex siRNA delivery.
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Retromer-Mediated Protein Sorting and Vesicular Trafficking
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作者 Jia-Jia Liu 《Journal of Genetics and Genomics》 SCIE CAS CSCD 2016年第4期165-177,共13页
Retromer is an evolutionarily conserved multimeric protein complex that mediates intracellular transport of various vesicular cargoes and functions in a wide variety of cellular processes including polarized trafficki... Retromer is an evolutionarily conserved multimeric protein complex that mediates intracellular transport of various vesicular cargoes and functions in a wide variety of cellular processes including polarized trafficking,developmental signaling and lysosome biogenesis.Through its interaction with the Rab GTPases and their effectors,membrane lipids,molecular motors,the endocytic machinery and actin nucleation promoting factors,retromer regulates sorting and trafficking of transmembrane proteins from endosomes to the trans-Golgi network(TGN) and the plasma membrane.In this review.I highlight recent progress in the understanding of relromer-medialed protein sorting and vesicle trafficking and discuss how retromer contributes to a diverse set of developmental,physiological and pathological processes. 展开更多
关键词 RETROMER Sorting nexin endosome Protein sorting and trafficking NEURODEGENERATION
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pH-responsive magnesium- and carbonate-substituted apatite nano-crystals for efficient and cell-targeted delivery of transgenes
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作者 Ezharul Hoque Chowdhury 《Open Journal of Genetics》 2013年第2期38-44,共7页
The short half-lives due to the enzymatic degradation in blood, the lack of tissue targetability and the incapability to passively diffuse across the plasma membrane and smoothly traffic across the harsh intracelluar ... The short half-lives due to the enzymatic degradation in blood, the lack of tissue targetability and the incapability to passively diffuse across the plasma membrane and smoothly traffic across the harsh intracelluar environment are the major shortcomings for nucleic acid-based potential therapeutics, such as recombinant plasmid and antisense oligonucleotides or small interferring RNA (siRNA). Plasmid DNA containing a gene of interest could have immense impact as a promising therapeutic drug for treating genetic as well as acquired human diseases at the molecular level with high level of efficacy and precision. Thus both viral and non-viral synthetic vectors have been developed in the past decades to address the aforementioned challenges of naked DNA. While in the viral particles plasmid DNA is integrated into the viral genome, in most non-viral cases the DNA being anionic in nature is electrostatically associated with a cationic lipid or polymer forming lipoplex or polyplex, respectively, or a cationized inorganic gold, silica or iron oxide particle. Due to the potential immunogenicity and carcinogenicity issues with the viral particles, non-viral vectors have drawn much more attention for the clinical evaluation. However, the main concern of using non-biodegradable particles, specially the inorganic ones, is the adverse effects owing to their long term interactions with body components. We have recently developed biodegradable pH-sensitive inorganic nanoparticles of Mg/CaPi and carbonate apatite for efficient transgene delivery to primary, cancer and embryonic stem cells, by virtue of their high affinity binding with the DNA, ability to contact the cell membrane by ionic or ligand-receptor interactions and fast dissolution kinectis in endosomal acidic pH facilitating release of the DNA from the dissolving particles and also from the endosomes. 展开更多
关键词 GENE Therapy Nanoparticles Particle Dissolution Ca/Mgpi CARBONATE APATITE endosome Nucleus GENE Expression
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