共查询到20条相似文献，搜索用时 31 毫秒
1.
Kwon YT Kashina AS Davydov IV Hu RG An JY Seo JW Du F Varshavsky A 《Science (New York, N.Y.)》2002,297(5578):96-99
The enzymatic conjugation of arginine to the N-termini of proteins is a part of the ubiquitin-dependent N-end rule pathway of protein degradation. In mammals, three N-terminal residues-aspartate, glutamate, and cysteine-are substrates for arginylation. The mouse ATE1 gene encodes a family of Arg-tRNA-protein transferases (R-transferases) that mediate N-terminal arginylation. We constructed ATE1-lacking mouse strains and found that ATE1-/- embryos die with defects in heart development and in angiogenic remodeling of the early vascular plexus. Through biochemical analyses, we show that N-terminal cysteine, in contrast to N-terminal aspartate and glutamate, is oxidized before its arginylation by R-transferase, suggesting that the arginylation branch of the N-end rule pathway functions as an oxygen sensor. 相似文献
2.
Zicha D Dobbie IM Holt MR Monypenny J Soong DY Gray C Dunn GA 《Science (New York, N.Y.)》2003,300(5616):142-145
Transformed rat fibroblasts expressing two variants of green fluorescent protein, each fused to beta-actin, were used to study actin dynamics during cell protrusion. The recently developed FLAP (fluorescence localization after photobleaching) method permits the tracking of one fluorophore after localized photobleaching by using the other as a colocalized reference. Here, by visualizing the ratio of bleached to total molecules, we found that actin was delivered to protruding zones of the leading edge of the cell at speeds that exceeded 5 micrometers per second. Monte Carlo modeling confirmed that this flow cannot be explained by diffusion and may involve active transport. 相似文献
3.
The actin-binding protein profilin binds to PIP2 and inhibits its hydrolysis by phospholipase C 总被引：41，自引：0，他引：41
P J Goldschmidt-Clermont L M Machesky J J Baldassare T D Pollard 《Science (New York, N.Y.)》1990,247(4950):1575-1578
Profilin is generally thought to regulate actin polymerization, but the observation that acidic phospholipids dissociate the complex of profilin and actin raised the possibility that profilin might also regulate lipid metabolism. Profilin isolated from platelets binds with high affinity to small clusters of phosphatidylinositol 4,5-bisphosphate (PIP2) molecules in micelles and also in bilayers with other phospholipids. The molar ratio of the complex of profilin with PIP2 is 1:7 in micelles of pure PIP2 and 1:5 in bilayers composed largely of other phospholipids. Profilin competes efficiently with platelet cytosolic phosphoinositide-specific phospholipase C for interaction with the PIP2 substrate and thereby inhibits PIP2 hydrolysis by this enzyme. The cellular concentrations and binding characteristics of these molecules are consistent with profilin being a negative regulator of the phosphoinositide signaling pathway in addition to its established function as an inhibitor of actin polymerization. 相似文献
4.
Entry of the bacterium Salmonella typhimurium into host cells requires membrane ruffling and rearrangement of the actin cytoskeleton. Here, it is shown that the bacterial protein SipA plays a critical role in this process. SipA binds directly to actin, decreases its critical concentration, and inhibits depolymerization of actin filaments. These activities result in the spatial localization and more pronounced outward extension of the Salmonella-induced membrane ruffles, thereby facilitating bacterial uptake. 相似文献
5.
Gu Y Filippi MD Cancelas JA Siefring JE Williams EP Jasti AC Harris CE Lee AW Prabhakar R Atkinson SJ Kwiatkowski DJ Williams DA 《Science (New York, N.Y.)》2003,302(5644):445-449
The Rho guanosine triphosphatases (GTPases) Rac1 and Rac2 are critical signaling regulators in mammalian cells. The deletion of both Rac1 and Rac2 murine alleles leads to a massive egress of hematopoietic stem/progenitor cells (HSC/Ps) into the blood from the marrow, whereas Rac1-/- but not Rac2-/- HSC/Ps fail to engraft in the bone marrow of irradiated recipient mice. In contrast, Rac2, but not Rac1, regulates superoxide production and directed migration in neutrophils, and in each cell type, the two GTPases play distinct roles in actin organization, cell survival, and proliferation. Thus, Rac1 and Rac2 regulate unique aspects of hematopoietic development and function. 相似文献
6.
Essential regulation of CNS angiogenesis by the orphan G protein-coupled receptor GPR124 总被引：1，自引：0，他引：1
Kuhnert F Mancuso MR Shamloo A Wang HT Choksi V Florek M Su H Fruttiger M Young WL Heilshorn SC Kuo CJ 《Science (New York, N.Y.)》2010,330(6006):985-989
The orphan G protein-coupled receptor (GPCR) GPR124/tumor endothelial marker 5 is highly expressed in central nervous system (CNS) endothelium. Here, we show that complete null or endothelial-specific GPR124 deletion resulted in embryonic lethality from CNS-specific angiogenesis arrest in forebrain and neural tube. Conversely, GPR124 overexpression throughout all adult vascular beds produced CNS-specific hyperproliferative vascular malformations. In vivo, GPR124 functioned cell-autonomously in endothelium to regulate sprouting, migration, and developmental expression of the blood-brain barrier marker Glut1, whereas in vitro, GPR124 mediated Cdc42-dependent directional migration to forebrain-derived, vascular endothelial growth factor-independent cues. Our results demonstrate CNS-specific angiogenesis regulation by an endothelial receptor and illuminate functions of the poorly understood adhesion GPCR subfamily. Further, the functional tropism of GPR124 marks this receptor as a therapeutic target for CNS-related vascular pathologies. 相似文献
7.
Viviani D Charlet A van den Burg E Robinet C Hurni N Abatis M Magara F Stoop R 《Science (New York, N.Y.)》2011,333(6038):104-107
Central amygdala (CeA) projections to hypothalamic and brain stem nuclei regulate the behavioral and physiological expression of fear, but it is unknown whether these different aspects of the fear response can be separately regulated by the CeA. We combined fluorescent retrograde tracing of CeA projections to nuclei that modulate fear-related freezing or cardiovascular responses with in vitro electrophysiological recordings and with in vivo monitoring of related behavioral and physiological parameters. CeA projections emerged from separate neuronal populations with different electrophysiological characteristics and different response properties to oxytocin. In vivo, oxytocin decreased freezing responses in fear-conditioned rats without affecting the cardiovascular response. Thus, neuropeptidergic signaling can modulate the CeA outputs through separate neuronal circuits and thereby individually steer the various aspects of the fear response. 相似文献
8.
胞间连丝是植物体内连接相邻细胞的一种跨细胞的细胞器,是细胞间物质运输和信息传递的通道,为相邻细胞间小分子、病毒颗粒及一些特殊大分子的运输提供途径。细胞间的共质通道就在质膜和其内部的压缩内质网间形成,压缩内质网又称连丝微管。由于胞间连丝结构的复杂性,使得对其结构组分的研究受到很大限制,但近几年随着电子显微镜、免疫标记、显微注射技术的广泛应用,已有证据表明肌动蛋白、肌球蛋白、中心蛋白和钙网蛋白等是胞间连丝的组分,这些蛋白之间相互作用调节胞间连丝的通透性,控制物质运输。 相似文献
9.
血管平滑肌细胞(vascular smooth muscle cells,VSMCs)是血管壁的主要构成组分。同时,VSMCs容易受到异常环境信号的影响,发生表型从收缩型向增殖型转化,从而导致以血管平滑肌细胞增生为特征的心血管疾病的发生及发展。因此,寻找调控VSMCs表型转化的天然活性物质,揭示其调控的分子机制非常重要。近年来的研究发现,多种植物天然活性产物可以调控血管平滑肌细胞表型转化,从而为筛选治疗心血管系统疾病的药物研发提供了基础。介绍了VSMCs的特性及其表型转化引起的相关心血管疾病,总结了调控VSMCs表型转化的植物天然活性产物,重点综述了近几年植物天然活性产物调控血管平滑肌细胞表型转化分子机制的研究进展。 相似文献
10.
Reymann AC Boujemaa-Paterski R Martiel JL Guérin C Cao W Chin HF De La Cruz EM Théry M Blanchoin L 《Science (New York, N.Y.)》2012,336(6086):1310-1314
The organization of actin filaments into higher-ordered structures governs eukaryotic cell shape and movement. Global actin network size and architecture are maintained in a dynamic steady state through regulated assembly and disassembly. Here, we used experimentally defined actin structures in vitro to investigate how the activity of myosin motors depends on network architecture. Direct visualization of filaments revealed myosin-induced actin network deformation. During this reorganization, myosins selectively contracted and disassembled antiparallel actin structures, while parallel actin bundles remained unaffected. The local distribution of nucleation sites and the resulting orientation of actin filaments appeared to regulate the scalability of the contraction process. This "orientation selection" mechanism for selective contraction and disassembly suggests how the dynamics of the cellular actin cytoskeleton can be spatially controlled by actomyosin contractility. 相似文献
11.
松江鲈β-肌动蛋白基因全长cDNA的克隆和序列分析 总被引：1，自引：0，他引：1
[目的]获得松江鲈β-肌动蛋白基因cDNA全长序列,并检测松江鲈β-肌动蛋白在组织中的表达。[方法]以松江鲈肌肉总RNA为模板,采用RT-PCR、5′-RACE和3′-RACE的方法扩增β-肌动蛋白基因cDNA片段,用RT-PCR方法检测组织表达。[结果]获得了松江鲈β-肌动蛋白基因cDNA的3个片段,测序后拼接得到1905bp全长cDNA序列,其包含了1128个核苷酸的开放性阅读框,翻译编码375个氨基酸。核苷酸和氨基酸同源性分析发现,松江鲈β-肌动蛋白基因序列与点带石斑鱼、军曹鱼、红鲷鱼等同源性相对较高,与哺乳动物和鸟类同源性相对较低;系统发育分析表明,松江鲈β-肌动蛋白与点带石斑鱼关系最近。RT-PCR分析表明,该基因在检测的肌肉、肝脏、肠和脑4种组织均有表达。[结论]首次得到了β-肌动蛋白基因cDNA全长序列,并证明了松江鲈的β-肌动蛋白基因非常保守。 相似文献
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[目的]获得松江鲈β-肌动蛋白基因cDNA全长序列,并检测松江鲈β-肌动蛋白在组织中的表达。[方法]以松江鲈肌肉总RNA为模板,采用RT-PCR、5′-RACE和3′-RACE的方法扩增β-肌动蛋白基因cDNA片段,用RT-PCR方法检测组织表达。[结果]获得了松江鲈β-肌动蛋白基因cDNA的3个片段,测序后拼接得到1 905 bp全长cDNA序列,其包含了1 128个核苷酸的开放性阅读框,翻译编码375个氨基酸。核苷酸和氨基酸同源性分析发现,松江鲈β-肌动蛋白基因序列与点带石斑鱼、军曹鱼、红鲷鱼等同源性相对较高,与哺乳动物和鸟类同源性相对较低;系统发育分析表明,松江鲈β-肌动蛋白与点带石斑鱼关系最近。RT-PCR分析表明,该基因在检测的肌肉、肝脏、肠和脑4种组织均有表达。[结论]首次得到了β-肌动蛋白基因cDNA全长序列,并证明了松江鲈的β-肌动蛋白基因非常保守。 相似文献
14.
Alvarez JI Dodelet-Devillers A Kebir H Ifergan I Fabre PJ Terouz S Sabbagh M Wosik K Bourbonnière L Bernard M van Horssen J de Vries HE Charron F Prat A 《Science (New York, N.Y.)》2011,334(6063):1727-1731
The blood-brain barrier (BBB) is composed of tightly bound endothelial cells (ECs) and perivascular astrocytes that regulate central nervous system (CNS) homeostasis. We showed that astrocytes secrete Sonic hedgehog and that BBB ECs express Hedgehog (Hh) receptors, which together promote BBB formation and integrity during embryonic development and adulthood. Using pharmacological inhibition and genetic inactivation of the Hh signaling pathway in ECs, we also demonstrated a critical role of the Hh pathway in promoting the immune quiescence of BBB ECs by decreasing the expression of proinflammatory mediators and the adhesion and migration of leukocytes, in vivo and in vitro. Overall, the Hh pathway provides a barrier-promoting effect and an endogenous anti-inflammatory balance to CNS-directed immune attacks, as occurs in multiple sclerosis. 相似文献
15.
Lamellipodia are thin, veil-like extensions at the edge of cells that contain a dynamic array of actin filaments. We describe an approach for analyzing spatial regulation of actin polymerization and depolymerization in vivo in which we tracked single molecules of actin fused to the green fluorescent protein. Polymerization and the lifetime of actin filaments in lamellipodia were measured with high spatial precision. Basal polymerization and depolymerization occurred throughout lamellipodia with largely constant kinetics, and polymerization was promoted within one micron of the lamellipodium tip. Most of the actin filaments in the lamellipodium were generated by polymerization away from the tip. 相似文献
16.
Ghosh M Song X Mouneimne G Sidani M Lawrence DS Condeelis JS 《Science (New York, N.Y.)》2004,304(5671):743-746
A general caging method for proteins that are regulated by phosphorylation was used to study the in vivo biochemical action of cofilin and the subsequent cellular response. By acute and local activation of a chemically engineered, light-sensitive phosphocofilin mimic, we demonstrate that cofilin polymerizes actin, generates protrusions, and determines the direction of cell migration. We propose a role for cofilin that is distinct from its role as an actin-depolymerizing factor. 相似文献
17.
The role of localized instability of the actin network in specifying axonal fate was examined with the use of rat hippocampal neurons in culture. During normal neuronal development, actin dynamics and instability polarized to a single growth cone before axon formation. Consistently, global application of actin-depolymerizing drugs and of the Rho-signaling inactivator toxin B to nonpolarized cells produced neurons with multiple axons. Moreover, disruption of the actin network in one individual growth cone induced its neurite to become the axon. Thus, local instability of the actin network restricted to a single growth cone is a physiological signal specifying neuronal polarization. 相似文献
18.
Different types of cell behavior, including growth, motility, and navigation, require actin proteins to assemble into filaments. Here, we describe a biochemical process that was able to disassemble actin filaments and limit their reassembly. Actin was a specific substrate of the multidomain oxidation-reduction enzyme, Mical, a poorly understood actin disassembly factor that directly responds to Semaphorin/Plexin extracellular repulsive cues. Actin filament subunits were directly modified by Mical on their conserved pointed-end, which is critical for filament assembly. Mical posttranslationally oxidized the methionine 44 residue within the D-loop of actin, simultaneously severing filaments and decreasing polymerization. This mechanism underlying actin cytoskeletal collapse may have broad physiological and pathological ramifications. 相似文献
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Kawasaki Y Senda T Ishidate T Koyama R Morishita T Iwayama Y Higuchi O Akiyama T 《Science (New York, N.Y.)》2000,289(5482):1194-1197
The adenomatous polyposis coli gene (APC) is mutated in familial adenomatous polyposis and in sporadic colorectal tumors. Here the APC gene product is shown to bind through its armadillo repeat domain to a Rac-specific guanine nucleotide exchange factor (GEF), termed Asef. Endogenous APC colocalized with Asef in mouse colon epithelial cells and neuronal cells. Furthermore, APC enhanced the GEF activity of Asef and stimulated Asef-mediated cell flattening, membrane ruffling, and lamellipodia formation in MDCK cells. These results suggest that the APC-Asef complex may regulate the actin cytoskeletal network, cell morphology and migration, and neuronal function. 相似文献