In the ongoing process of uncovering molecular abnormalities in neurodegenerative diseases characterized by toxic protein aggregates,nucleo-cytoplasmic transport defects have an emerging role.Several pieces of evidenc...In the ongoing process of uncovering molecular abnormalities in neurodegenerative diseases characterized by toxic protein aggregates,nucleo-cytoplasmic transport defects have an emerging role.Several pieces of evidence suggest a link between neuronal protein inclusions and nuclear pore complex(NPC)damage.These processes lead to oxidative stress,inefficient transcription,and aberrant DNAVRNA maintenance.The clinical and neuropathological spectrum of NPC defects is broad,ranging from physiological aging to a suite of neurodegenerative diseases.A better understanding of the shared pathways among these conditions may represent a significant step toward dissecting their underlying molecular mechanisms,opening the way to a real possibility of identifying common therapeutic targets.展开更多
The developmental fate of the pronuclei in recombined embryos obtained by transplanting the donor nuclei into the non-enucleated eggs remains controversial in the case of fish. In the present study, the nuclei from th...The developmental fate of the pronuclei in recombined embryos obtained by transplanting the donor nuclei into the non-enucleated eggs remains controversial in the case of fish. In the present study, the nuclei from the loach blastulae were transplanted into non-enucleated zebrafish eggs, the resulting 9 inter-family nuclear transplant embryos developed to larval stages. Although the development timing of the nuclear transplants resembled that of zebrafish, chromosome examination revealed that most of the recombined embryos were diploids with karyotype characteristic of loach, which was also proved by RAPD analysis. Moreover, 3 out of the 9 larval fish formed barb rudiments specific to loach. It was therefore concluded that the nuclear transplant larval fish were inter-family nucleo-cytoplasmic hybrids; and that only the donor nuclei were involved in the development of the nuclear transplant embryos, while the pronuclei in the non-enucleated eggs were likely automatically eliminated during the development.展开更多
The phytohormone auxin plays a pivotal role in governing plant growth and development.Although the TRANSPORT INHIBITOR RESPONSE1/AUXIN SIGNALING F-BOX(TIR1/AFB)receptors function in both the nucleus and cytoplasm,the ...The phytohormone auxin plays a pivotal role in governing plant growth and development.Although the TRANSPORT INHIBITOR RESPONSE1/AUXIN SIGNALING F-BOX(TIR1/AFB)receptors function in both the nucleus and cytoplasm,the mechanism governing the distribution of TIR1/AFBs between these cellular compartments remains unknown.In this study,we demonstrate that auxin-mediated oxidation of TIR1/AFB2 is essential for their targeting to the nucleus.We showed that small active molecules,reactive oxygen species(ROS)and nitric oxide(NO),are indispensable for the nucleo-cytoplasmic distribution of TIR1/AFB2 in trichoblasts and root hairs.Further studies revealed that this process is regulated by the FERONIA receptor kinase–NADPH oxidase signaling pathway.Interestingly,ROS and NO initiate oxidative modifications in TIR1C140/516 and AFB2C135/511,facilitating their subsequent nuclear import.The oxidized forms of TIR1C140/516 and AFB2C135/511 play a crucial role in enhancing the function of TIR1 and AFB2 in transcriptional auxin responses.Collectively,our study reveals a novel mechanism by which auxin stimulates the transport of TIR1/AFB2 from the cytoplasm to the nucleus,orchestrated by the FERONIA–ROS signaling pathway.展开更多
The mammalian nuclear pore complex is comprised of∼30 different nucleoporins(Nups).It governs the nuclear import of gene expression modulators and the export of mRNAs.In cardiomyocytes,Na1-H1 exchanger-1(NHE1)is an i...The mammalian nuclear pore complex is comprised of∼30 different nucleoporins(Nups).It governs the nuclear import of gene expression modulators and the export of mRNAs.In cardiomyocytes,Na1-H1 exchanger-1(NHE1)is an integral membrane protein that exclusively regulates intracellular pH(pHi)by exchanging one intracellular H1 for one extracellular Na1.However,the role of Nups in cardiac NHE1 expression remains unknown.We herein report that Nup35 regulates cardiomyocyte NHE1 expression by controlling the nucleo-cytoplasmic trafficking of nhe1 mRNA.The N-terminal domain of Nup35 determines nhe1 mRNA nuclear export by targeting the 5′-UTR(2412 to2213 nt)of nhe1mRNA.Nup35 ablationweakensthe resistance of cardiomyocytes to an acid challenge by depressingNHE1 expression.Moreover,we identify thatNup35 andNHE1 are simultaneously downregulated in ischemic cardiomyocytes both in vivo and in vitro.Enforced expression of Nup35 effectively counteracts the anoxia-induced intracellular acidification.We conclude that Nup35 selectively regulates cardiomyocyte pHi homeostasis by posttranscriptionally controlling NHE1 expression.This finding reveals a novel regulatory mechanism of cardiomyocyte pHi,and may provide insight into the therapeutic strategy for ischemic cardiac diseases.展开更多
Background and Aims:Ras-related nuclear(RAN)protein is a small GTP-binding protein that is indispensable for the translocation of RNA and proteins through the nuclear pore complex.Recent studies have indicated that RA...Background and Aims:Ras-related nuclear(RAN)protein is a small GTP-binding protein that is indispensable for the translocation of RNA and proteins through the nuclear pore complex.Recent studies have indicated that RAN plays an important role in virus infection.However,the role of RAN in hepatitis C virus(HCV)infection is unclear.The objective of this study was to investigate the role and underlying mechanisms of RAN in HCV infection.Methods:Huh7.5.1 cells were infected with the JC1-Luc virus for 24 h and then were incubated with complete medium for an additional 48 h.HCV infection and RAN expression were determined using luciferase assay,quantitative reverse transcription-PCR and western blotting.Small interfering RNA was used to silence RAN.Western blotting and immunofluorescence were used to evaluate the cytoplasmic translocation of polypyrimidine tract-binding(PTB),and coimmunoprecipitation was used to examine the interaction between RAN and PTB.Results:HCV infection significantly induced RAN expression and cytoplasmic redistribution of PTB.Knockdown of RAN dramatically inhibited HCV infection and the cytoplasmic accumulation of PTB.Colocalization of RAN and PTB was determined by immunofluorescence,and a direct interaction of RAN with PTB was demonstrated by coimmunoprecipitation.Conclusions:PTB in the host cytoplasm is directly associated with HCV replication.These findings demonstrate that the involvement of RAN in HCV infection is mediated by influencing the cytoplasmic translocation of PTB.展开更多
文摘In the ongoing process of uncovering molecular abnormalities in neurodegenerative diseases characterized by toxic protein aggregates,nucleo-cytoplasmic transport defects have an emerging role.Several pieces of evidence suggest a link between neuronal protein inclusions and nuclear pore complex(NPC)damage.These processes lead to oxidative stress,inefficient transcription,and aberrant DNAVRNA maintenance.The clinical and neuropathological spectrum of NPC defects is broad,ranging from physiological aging to a suite of neurodegenerative diseases.A better understanding of the shared pathways among these conditions may represent a significant step toward dissecting their underlying molecular mechanisms,opening the way to a real possibility of identifying common therapeutic targets.
文摘The developmental fate of the pronuclei in recombined embryos obtained by transplanting the donor nuclei into the non-enucleated eggs remains controversial in the case of fish. In the present study, the nuclei from the loach blastulae were transplanted into non-enucleated zebrafish eggs, the resulting 9 inter-family nuclear transplant embryos developed to larval stages. Although the development timing of the nuclear transplants resembled that of zebrafish, chromosome examination revealed that most of the recombined embryos were diploids with karyotype characteristic of loach, which was also proved by RAPD analysis. Moreover, 3 out of the 9 larval fish formed barb rudiments specific to loach. It was therefore concluded that the nuclear transplant larval fish were inter-family nucleo-cytoplasmic hybrids; and that only the donor nuclei were involved in the development of the nuclear transplant embryos, while the pronuclei in the non-enucleated eggs were likely automatically eliminated during the development.
基金supported by grants from the National Natural Science Foundation of China(32230009,31770307,31972863)the Science and Technology Innovation Plan Of Shanghai Science and Technology Commission(20ZR1416500).
文摘The phytohormone auxin plays a pivotal role in governing plant growth and development.Although the TRANSPORT INHIBITOR RESPONSE1/AUXIN SIGNALING F-BOX(TIR1/AFB)receptors function in both the nucleus and cytoplasm,the mechanism governing the distribution of TIR1/AFBs between these cellular compartments remains unknown.In this study,we demonstrate that auxin-mediated oxidation of TIR1/AFB2 is essential for their targeting to the nucleus.We showed that small active molecules,reactive oxygen species(ROS)and nitric oxide(NO),are indispensable for the nucleo-cytoplasmic distribution of TIR1/AFB2 in trichoblasts and root hairs.Further studies revealed that this process is regulated by the FERONIA receptor kinase–NADPH oxidase signaling pathway.Interestingly,ROS and NO initiate oxidative modifications in TIR1C140/516 and AFB2C135/511,facilitating their subsequent nuclear import.The oxidized forms of TIR1C140/516 and AFB2C135/511 play a crucial role in enhancing the function of TIR1 and AFB2 in transcriptional auxin responses.Collectively,our study reveals a novel mechanism by which auxin stimulates the transport of TIR1/AFB2 from the cytoplasm to the nucleus,orchestrated by the FERONIA–ROS signaling pathway.
基金This work was supported by grants from the National Key Basic Research Program of China(2013CB531100 to Y.-H.C.)the National Natural Science Foundation of China for National Innovative Research Groups(81221001 to Y.-H.C.)+2 种基金the Major International Joint Research Program of China(81120108004 to Y.-H.C.)the Youth Program(81100124 to L.X.)the General Program(81170224 and 81270313 to J.L.and 31271214 to Y.-H.C.)of the National Natural Science Foundation of China.
文摘The mammalian nuclear pore complex is comprised of∼30 different nucleoporins(Nups).It governs the nuclear import of gene expression modulators and the export of mRNAs.In cardiomyocytes,Na1-H1 exchanger-1(NHE1)is an integral membrane protein that exclusively regulates intracellular pH(pHi)by exchanging one intracellular H1 for one extracellular Na1.However,the role of Nups in cardiac NHE1 expression remains unknown.We herein report that Nup35 regulates cardiomyocyte NHE1 expression by controlling the nucleo-cytoplasmic trafficking of nhe1 mRNA.The N-terminal domain of Nup35 determines nhe1 mRNA nuclear export by targeting the 5′-UTR(2412 to2213 nt)of nhe1mRNA.Nup35 ablationweakensthe resistance of cardiomyocytes to an acid challenge by depressingNHE1 expression.Moreover,we identify thatNup35 andNHE1 are simultaneously downregulated in ischemic cardiomyocytes both in vivo and in vitro.Enforced expression of Nup35 effectively counteracts the anoxia-induced intracellular acidification.We conclude that Nup35 selectively regulates cardiomyocyte pHi homeostasis by posttranscriptionally controlling NHE1 expression.This finding reveals a novel regulatory mechanism of cardiomyocyte pHi,and may provide insight into the therapeutic strategy for ischemic cardiac diseases.
基金The work was supported by the Anhui Provincial Natural Science Foundation(1608085QH172)States S&T Projects of 13th Five Year(2018ZX10302206),Chinese Founda-tion for Hepatitis Prevention and Control(TQGB20200151,TQGB20180367)Anhui Key Program of Medical Scien-tific Research of China(#2010A010).
文摘Background and Aims:Ras-related nuclear(RAN)protein is a small GTP-binding protein that is indispensable for the translocation of RNA and proteins through the nuclear pore complex.Recent studies have indicated that RAN plays an important role in virus infection.However,the role of RAN in hepatitis C virus(HCV)infection is unclear.The objective of this study was to investigate the role and underlying mechanisms of RAN in HCV infection.Methods:Huh7.5.1 cells were infected with the JC1-Luc virus for 24 h and then were incubated with complete medium for an additional 48 h.HCV infection and RAN expression were determined using luciferase assay,quantitative reverse transcription-PCR and western blotting.Small interfering RNA was used to silence RAN.Western blotting and immunofluorescence were used to evaluate the cytoplasmic translocation of polypyrimidine tract-binding(PTB),and coimmunoprecipitation was used to examine the interaction between RAN and PTB.Results:HCV infection significantly induced RAN expression and cytoplasmic redistribution of PTB.Knockdown of RAN dramatically inhibited HCV infection and the cytoplasmic accumulation of PTB.Colocalization of RAN and PTB was determined by immunofluorescence,and a direct interaction of RAN with PTB was demonstrated by coimmunoprecipitation.Conclusions:PTB in the host cytoplasm is directly associated with HCV replication.These findings demonstrate that the involvement of RAN in HCV infection is mediated by influencing the cytoplasmic translocation of PTB.
