Actin cytoskeleton dynamics is critical for variety of cellular events including cell elongation, division and morphogenesis, and is tightly regulated by numerous groups of actin binding proteins. However it is not we...Actin cytoskeleton dynamics is critical for variety of cellular events including cell elongation, division and morphogenesis, and is tightly regulated by numerous groups of actin binding proteins. However it is not well understood how these actin binding proteins are modulated in a physiological condition by their interaction proteins. In this study, we describe that Arabidopsis 14-3-3 λ protein interacted with actin depolymerizing factor 1(ADF1) in plant to regulate F-actin stability and dynamics. Loss of 14-3-3 λin Arabidopsis resulted in longer etiolated hypocotyls in dark and changed actin cytoskeleton architecture in hypocotyl cells. Overexpression of ADF1 repressed 14-3-3 λ mutant hypocotyl elongation and actin dynamic phenotype. In addition, the phosphorylation level of ADF1 was increased and the subcellular localization of ADF1 was altered in 14-3-3 λ mutant. Consistent with these observations, the actin filaments were more stable in 14-3-3 λ mutant. Our results indicate that 14-3-3 λ protein mediates F-actin dynamics possibly through inhibiting ADF1 phosphorylation in vivo.展开更多
Anticancer drugs are one of the most direct means of cancer therapy.However,the various cancer progressions hamper the development and discovery of anticancer drugs.In fact,the mechanical properties of the tumor cytos...Anticancer drugs are one of the most direct means of cancer therapy.However,the various cancer progressions hamper the development and discovery of anticancer drugs.In fact,the mechanical properties of the tumor cytoskeleton are extremely vital for any phase of cancer,especially in tumor invasion and metastasis.However,in the current category of anticancer drugs,the cytoskeleton-targeting drugs are limited and their role in tumor progression is unclear.Here,we present the mechanical characteristics of tumor stiffness that are tightly regulated by the cancer cytoskeleton,including actin filaments and microtubules during tumor initiation,growth and metastasis,and review the natural drugs that target the cancer cytoskeleton.We define cytoskeleton dynamics as target mechanisms for anticancer drugs and summarize the plant,microbial and marine sources of natural products.Furthermore,this paper also provides a material pathway to study active tumor mechanics,and introduces the unique advantages and future application potential of tumor cytoskeleton-targeting drugs in clinical use.The material approaches to active cancer mechanics are supplied in this review.We aim to promote the development of anticancer drugs that target tumor mechanics by using those material approaches and finding their pharmacological application.展开更多
Melanoma Differentiation-Associated gene 5(MDA5)serves as a pattern recognition receptor(PRR)that identifies pathogen-associated molecular patterns(PAMPs),making it instrumental in antiviral defense.However,its non-ca...Melanoma Differentiation-Associated gene 5(MDA5)serves as a pattern recognition receptor(PRR)that identifies pathogen-associated molecular patterns(PAMPs),making it instrumental in antiviral defense.However,its non-canonical role in adaptive immunity,particularly in regulating B-cell immune functions,is poorly characterized.Here,we demonstrate that MDA5 is critical for the marginal zone(MZ)B-cell differentiation,B-cell receptor(BCR)signal transduction,and cytoskeletal dynamics.We determined that the MDA5-NF-κB-DNM1 axis governs actin polymerization and that this impairment in Mda5 knockout(KO)B cells can be rescued by the treatment with the dynamin1(DNM1)activator Bis-T-23.Furthermore,MDA5 deficiency induces metabolic perturbations in B cells,characterized by a reduced extracellular acidification rate(ECAR)and oxygen consumption rate(OCR),excessive reactive oxygen species(ROS)accumulation,and increased mitochondrial fission.Notably,taurine levels are decreased in Mda5 KO B cells,and in vitro taurine supplementation rescues impaired BCR signaling.Finally,MDA5-deficient mice exhibit a blunted humoral immune response.Overall,this study reveals the key functions and molecular mechanisms of MDA5 in B-cell differentiation,BCR signaling,and the humoral immune response.展开更多
In this review, we address the question of how the tip-growing pollen tube achieves its rapid rate of elongation while maintaining an intact cell wall. Although turgor is essential for growth to occur, the local expan...In this review, we address the question of how the tip-growing pollen tube achieves its rapid rate of elongation while maintaining an intact cell wall. Although turgor is essential for growth to occur, the local expansion rate is controlled by local changes in the viscosity of the apical wall. We focus on several different structures and underly- ing processes that are thought to be major participants including exocytosis, the organization and activity of the actin cytoskeleton, calcium and proton physiology, and cellular energetics. We think that the actin cytoskeleton, in particular the apical cortical actin fringe, directs the flow of vesicles to the apical domain, where they fuse with the plasma mem- brane and contribute their contents to the expanding cell wall. While pH gradients, as generated by a proton-ATPase located on the plasma membrane along the side of the clear zone, may regulate rapid actin turnover and new polymeri- zation in the fringe, the tip-focused calcium gradient biases secretion towards the polar axis. The recent data showing that exocytosis of new wall material precedes and predicts the process of cell elongation provide support for the idea that the intussusception of newly secreted pectin contributes to decreases in apical wall viscosity and to cell expansion. Other prime factors will be the localization and activity of the enzyme pectin methyl-esterase, and the chelation of calcium by pectic acids. Finally, we acknowledge a role for reactive oxygen species in the control of wall viscosity.展开更多
Radially arranged cortical microtubules are a prominent feature of guard cells. Guard cells expressing GFP- tubulin showed consistent changes in the appearance of microtubules when stomata opened or closed. Guard cell...Radially arranged cortical microtubules are a prominent feature of guard cells. Guard cells expressing GFP- tubulin showed consistent changes in the appearance of microtubules when stomata opened or closed. Guard cells showed fewer microtubule structures as stomata closed, whether induced by transfer to darkness, ABA, hydrogen per- oxide, or sodium hydrogen carbonate. Guard cells kept in the dark （closed stomata） showed increases in microtubule struc- tures and stomatal aperture on light treatment. GFP-EB1, marking microtubule growing plus ends, showed no change in number of plus ends or velocity of assembly on stomatal closure. Since the number of growing plus ends and the rate of plus-end growth did not change when microtubule structure numbers declined, microtubule instability and/or rearrange- ment must be responsible for the apparent loss of microtubules. Guard cells with closed stomata showed more cytosolic GFP-fluorescence than those with open stomata as cortical microtubules became disassembled, although with a large net loss in total fluorescence. Microtubule-targeted drugs blocked guard-cell function in Vicia and Arabidopsis. Oryzalin dis- rupted guard-cell microtubules and prevented stomatal opening and taxol stabilized guard-cell microtubules and delayed stomatal closure. Gas exchange measurements indicated that the transgenes for fluorescent-labeled proteins did not dis- rupt normal stomatal function. These dynamic changes in guard-cell microtubules combined with our inhibitor studies provide evidence for an active role of microtubules in guard-cell function.展开更多
Chloroplast movement is essential for plants to survive under various environmental light conditions. Photo- tropins--plant-specific blue-light-activated receptor kinases--mediate the response by perceiving light inte...Chloroplast movement is essential for plants to survive under various environmental light conditions. Photo- tropins--plant-specific blue-light-activated receptor kinases--mediate the response by perceiving light intensity and direction. Recently, novel chloroplast actin （cp-actin） filaments have been identified as playing a pivotal role in the directional chloroplast photorelocation movement. Encouraging progress has recently been made in this field of research through molecular genetics and cell biological analyses. This review describes factors that have been identified as being involved in chloroplast movement and their roles in the regulation of cp-actin filaments, thus providing a basis for reflection on their biochemical activities and functions.展开更多
The actin cytoskeleton plays a role in mobility of many different organelles in plant cells, including chloroplasts, mitochondria, Golgi, and peroxisomes. While progress has been made in identifying the myosin motors ...The actin cytoskeleton plays a role in mobility of many different organelles in plant cells, including chloroplasts, mitochondria, Golgi, and peroxisomes. While progress has been made in identifying the myosin motors involved in trafficking of various plant organelles, not all of the cargoes mobilized by different members of the myosin XI family have yet been identified. The involvement of myosins in chloroplast positioning and mitochondrial movement was demonstrated by expression of a virus-induced gene silencing （VIGS） construct in tobacco. When VIGS with two different conserved sequences from a myosin Xl motor was performed in plants with either GFP-labeled plastids or mitochondria, chloroplast positioning in the dark was abnormal, and mitochondrial movement ceased. Because these and prior obser- vations have implicated a role for myosins and the actin cytoskeleton in plastid and stromule movement, we searched for myosin tail domains that could associate with plastids and stromules. While a yellow fluorescent protein （YFP） fusion with the entire tail region of myosin XI-F was usually found only in the cytoplasm, we observed that an Arabidopsis or Nicotiana benthamiana YFP：：myosin XI-F tail domain homologous to the yeast myo2p vacuole-binding domain associated with plastids and stromules after transient expression in N. benthamiana. Taken together, these observations implicate myosin motor proteins in dynamics of plastids and stromules.展开更多
Cellular organelles move within the cellular volume and the effect of the resulting drag forces on the liquid causes bulk movement in the cytosol. The movement of both organelles and cytosol leads to an overall motion...Cellular organelles move within the cellular volume and the effect of the resulting drag forces on the liquid causes bulk movement in the cytosol. The movement of both organelles and cytosol leads to an overall motion pattern called cytoplasmic streaming or cyclosis. This streaming enables the active and passive transport of molecules and orga- nelles between cellular compartments. Furthermore, the fusion and budding of vesicles with and from the plasma mem- brane （exo/endocytosis） allow for transport of material between the inside and the outside of the cell. In the pollen tube, cytoplasmic streaming and exo/endocytosis are very active and fulfill several different functions. In this review, we focus on the logistics of intracellular motion and transport processes as well as their biophysical underpinnings. We discuss various modeling attempts that have been performed to understand both long-distance shuttling and short-distance targeting of organelles. We show how the combination of mechanical and mathematical modeling with cell biological approaches has contributed to our understanding of intracellular transport logistics.展开更多
Spermatogenesis is a complicated and poorly understood process that relies on the precise regulation of the self-renewal and differentiation of spermatogonia. In many organisms, micro RNAs(mi RNAs) are involved in mul...Spermatogenesis is a complicated and poorly understood process that relies on the precise regulation of the self-renewal and differentiation of spermatogonia. In many organisms, micro RNAs(mi RNAs) are involved in multiple developmental processes as critical regulators of transcriptional and post-transcriptional gene silencing. This study investigated the expression pattern of mi RNAs in type B spermatogonia cells(BSc) and primary spermatocytes(PSc) of mice, using a high-throughput small RNA sequencing system. The results revealed that the expression levels of Let-7 family mi RNAs were remarkably high in both cell types. Furthermore, the expression levels of mi R-21, mi R-140-3p, mi R-103, mi R-30 a, mi R-101 b and mi R-99 b were decreased during the transformation from BSc to PSc. These mi RNAs target vital genes that participate in apoptosis, cell proliferation and differentiation, junction assembly and cell cycle regulation. These results highlight the indispensable role of mi RNAs in spermatogenesis.展开更多
基金supported by the National Basic Research Program of China(2012CB114200)Foundation for Innovative Research Group of the National Natural Science Foundation of China(31421062)
文摘Actin cytoskeleton dynamics is critical for variety of cellular events including cell elongation, division and morphogenesis, and is tightly regulated by numerous groups of actin binding proteins. However it is not well understood how these actin binding proteins are modulated in a physiological condition by their interaction proteins. In this study, we describe that Arabidopsis 14-3-3 λ protein interacted with actin depolymerizing factor 1(ADF1) in plant to regulate F-actin stability and dynamics. Loss of 14-3-3 λin Arabidopsis resulted in longer etiolated hypocotyls in dark and changed actin cytoskeleton architecture in hypocotyl cells. Overexpression of ADF1 repressed 14-3-3 λ mutant hypocotyl elongation and actin dynamic phenotype. In addition, the phosphorylation level of ADF1 was increased and the subcellular localization of ADF1 was altered in 14-3-3 λ mutant. Consistent with these observations, the actin filaments were more stable in 14-3-3 λ mutant. Our results indicate that 14-3-3 λ protein mediates F-actin dynamics possibly through inhibiting ADF1 phosphorylation in vivo.
基金funded by"Beijing Natural Science Foundation,grant number 6224060","Young Elite Scientists Sponsorship Program by BAST,grant number",BYESS2023192"Program of Beijing Municipal Education Commission,grant number KM202310020006"+1 种基金"Bejing University of Agriculture science and Technology innovation Sparkling support plan,grant number,BUA-HHXD2022007""2022 Research and Innovation ability improvement plan for young teachers of Beijing University of Agriculture,grant number QJKC2022028".
文摘Anticancer drugs are one of the most direct means of cancer therapy.However,the various cancer progressions hamper the development and discovery of anticancer drugs.In fact,the mechanical properties of the tumor cytoskeleton are extremely vital for any phase of cancer,especially in tumor invasion and metastasis.However,in the current category of anticancer drugs,the cytoskeleton-targeting drugs are limited and their role in tumor progression is unclear.Here,we present the mechanical characteristics of tumor stiffness that are tightly regulated by the cancer cytoskeleton,including actin filaments and microtubules during tumor initiation,growth and metastasis,and review the natural drugs that target the cancer cytoskeleton.We define cytoskeleton dynamics as target mechanisms for anticancer drugs and summarize the plant,microbial and marine sources of natural products.Furthermore,this paper also provides a material pathway to study active tumor mechanics,and introduces the unique advantages and future application potential of tumor cytoskeleton-targeting drugs in clinical use.The material approaches to active cancer mechanics are supplied in this review.We aim to promote the development of anticancer drugs that target tumor mechanics by using those material approaches and finding their pharmacological application.
基金supported by the National Natural Science Foundation of China(82371784,32311530061)the National Key Research and Development Program of China(2023YFC2507900,2023YFC2706300)+2 种基金R&D Program of Guangzhou Laboratory(SRPG22-006)State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases(2024ZZ10014)the Hubei Provincial Natural Science Foundation of China(Grant number:2024AFB634).
文摘Melanoma Differentiation-Associated gene 5(MDA5)serves as a pattern recognition receptor(PRR)that identifies pathogen-associated molecular patterns(PAMPs),making it instrumental in antiviral defense.However,its non-canonical role in adaptive immunity,particularly in regulating B-cell immune functions,is poorly characterized.Here,we demonstrate that MDA5 is critical for the marginal zone(MZ)B-cell differentiation,B-cell receptor(BCR)signal transduction,and cytoskeletal dynamics.We determined that the MDA5-NF-κB-DNM1 axis governs actin polymerization and that this impairment in Mda5 knockout(KO)B cells can be rescued by the treatment with the dynamin1(DNM1)activator Bis-T-23.Furthermore,MDA5 deficiency induces metabolic perturbations in B cells,characterized by a reduced extracellular acidification rate(ECAR)and oxygen consumption rate(OCR),excessive reactive oxygen species(ROS)accumulation,and increased mitochondrial fission.Notably,taurine levels are decreased in Mda5 KO B cells,and in vitro taurine supplementation rescues impaired BCR signaling.Finally,MDA5-deficient mice exhibit a blunted humoral immune response.Overall,this study reveals the key functions and molecular mechanisms of MDA5 in B-cell differentiation,BCR signaling,and the humoral immune response.
文摘In this review, we address the question of how the tip-growing pollen tube achieves its rapid rate of elongation while maintaining an intact cell wall. Although turgor is essential for growth to occur, the local expansion rate is controlled by local changes in the viscosity of the apical wall. We focus on several different structures and underly- ing processes that are thought to be major participants including exocytosis, the organization and activity of the actin cytoskeleton, calcium and proton physiology, and cellular energetics. We think that the actin cytoskeleton, in particular the apical cortical actin fringe, directs the flow of vesicles to the apical domain, where they fuse with the plasma mem- brane and contribute their contents to the expanding cell wall. While pH gradients, as generated by a proton-ATPase located on the plasma membrane along the side of the clear zone, may regulate rapid actin turnover and new polymeri- zation in the fringe, the tip-focused calcium gradient biases secretion towards the polar axis. The recent data showing that exocytosis of new wall material precedes and predicts the process of cell elongation provide support for the idea that the intussusception of newly secreted pectin contributes to decreases in apical wall viscosity and to cell expansion. Other prime factors will be the localization and activity of the enzyme pectin methyl-esterase, and the chelation of calcium by pectic acids. Finally, we acknowledge a role for reactive oxygen species in the control of wall viscosity.
文摘Radially arranged cortical microtubules are a prominent feature of guard cells. Guard cells expressing GFP- tubulin showed consistent changes in the appearance of microtubules when stomata opened or closed. Guard cells showed fewer microtubule structures as stomata closed, whether induced by transfer to darkness, ABA, hydrogen per- oxide, or sodium hydrogen carbonate. Guard cells kept in the dark （closed stomata） showed increases in microtubule struc- tures and stomatal aperture on light treatment. GFP-EB1, marking microtubule growing plus ends, showed no change in number of plus ends or velocity of assembly on stomatal closure. Since the number of growing plus ends and the rate of plus-end growth did not change when microtubule structure numbers declined, microtubule instability and/or rearrange- ment must be responsible for the apparent loss of microtubules. Guard cells with closed stomata showed more cytosolic GFP-fluorescence than those with open stomata as cortical microtubules became disassembled, although with a large net loss in total fluorescence. Microtubule-targeted drugs blocked guard-cell function in Vicia and Arabidopsis. Oryzalin dis- rupted guard-cell microtubules and prevented stomatal opening and taxol stabilized guard-cell microtubules and delayed stomatal closure. Gas exchange measurements indicated that the transgenes for fluorescent-labeled proteins did not dis- rupt normal stomatal function. These dynamic changes in guard-cell microtubules combined with our inhibitor studies provide evidence for an active role of microtubules in guard-cell function.
文摘Chloroplast movement is essential for plants to survive under various environmental light conditions. Photo- tropins--plant-specific blue-light-activated receptor kinases--mediate the response by perceiving light intensity and direction. Recently, novel chloroplast actin （cp-actin） filaments have been identified as playing a pivotal role in the directional chloroplast photorelocation movement. Encouraging progress has recently been made in this field of research through molecular genetics and cell biological analyses. This review describes factors that have been identified as being involved in chloroplast movement and their roles in the regulation of cp-actin filaments, thus providing a basis for reflection on their biochemical activities and functions.
文摘The actin cytoskeleton plays a role in mobility of many different organelles in plant cells, including chloroplasts, mitochondria, Golgi, and peroxisomes. While progress has been made in identifying the myosin motors involved in trafficking of various plant organelles, not all of the cargoes mobilized by different members of the myosin XI family have yet been identified. The involvement of myosins in chloroplast positioning and mitochondrial movement was demonstrated by expression of a virus-induced gene silencing （VIGS） construct in tobacco. When VIGS with two different conserved sequences from a myosin Xl motor was performed in plants with either GFP-labeled plastids or mitochondria, chloroplast positioning in the dark was abnormal, and mitochondrial movement ceased. Because these and prior obser- vations have implicated a role for myosins and the actin cytoskeleton in plastid and stromule movement, we searched for myosin tail domains that could associate with plastids and stromules. While a yellow fluorescent protein （YFP） fusion with the entire tail region of myosin XI-F was usually found only in the cytoplasm, we observed that an Arabidopsis or Nicotiana benthamiana YFP：：myosin XI-F tail domain homologous to the yeast myo2p vacuole-binding domain associated with plastids and stromules after transient expression in N. benthamiana. Taken together, these observations implicate myosin motor proteins in dynamics of plastids and stromules.
文摘Cellular organelles move within the cellular volume and the effect of the resulting drag forces on the liquid causes bulk movement in the cytosol. The movement of both organelles and cytosol leads to an overall motion pattern called cytoplasmic streaming or cyclosis. This streaming enables the active and passive transport of molecules and orga- nelles between cellular compartments. Furthermore, the fusion and budding of vesicles with and from the plasma mem- brane （exo/endocytosis） allow for transport of material between the inside and the outside of the cell. In the pollen tube, cytoplasmic streaming and exo/endocytosis are very active and fulfill several different functions. In this review, we focus on the logistics of intracellular motion and transport processes as well as their biophysical underpinnings. We discuss various modeling attempts that have been performed to understand both long-distance shuttling and short-distance targeting of organelles. We show how the combination of mechanical and mathematical modeling with cell biological approaches has contributed to our understanding of intracellular transport logistics.
基金supported by the National Natural Science Foundation of China(81170616,81072093,30671092,81302323,31100915)the Natural Science Foundation of Hebei Province(C2014209140,C2009001260,C2012401039,H2013209194,C2013209024)the Scientific and Technical Supporting Programs of Hebei Province(10276109D)
文摘Spermatogenesis is a complicated and poorly understood process that relies on the precise regulation of the self-renewal and differentiation of spermatogonia. In many organisms, micro RNAs(mi RNAs) are involved in multiple developmental processes as critical regulators of transcriptional and post-transcriptional gene silencing. This study investigated the expression pattern of mi RNAs in type B spermatogonia cells(BSc) and primary spermatocytes(PSc) of mice, using a high-throughput small RNA sequencing system. The results revealed that the expression levels of Let-7 family mi RNAs were remarkably high in both cell types. Furthermore, the expression levels of mi R-21, mi R-140-3p, mi R-103, mi R-30 a, mi R-101 b and mi R-99 b were decreased during the transformation from BSc to PSc. These mi RNAs target vital genes that participate in apoptosis, cell proliferation and differentiation, junction assembly and cell cycle regulation. These results highlight the indispensable role of mi RNAs in spermatogenesis.
