肺炎链球菌二元信号转导系统研究进展

肺炎链球菌是引起细菌性肺炎的主要病原菌。透彻地了解肺炎链球菌的信号转导对于系统地认识该菌的致病机制和靶标药物的设计具有重要意义。二元信号转导系统作为在病原菌中普遍存在的一种跨膜信号转导机制,在细菌响应外界环境变化并作出适应性反应的过程中起着主要作用。随着大规模基因组测序、信号标签诱变、差异荧光诱导以及DNA微阵列等技术的蓬勃发展,关于肺炎链球菌的二元信号转导系统已经取得了许多重要的研究成果。本文就肺炎链球菌二元信号转导系统的研究进展作一综述。     

猪链球菌2型89K毒力岛研究进展

高致病性猪链球菌2型的致病机制仍是未解之谜.毒力岛不仅赋予病原菌特殊的致病能力,而且在细菌的适应性进化过程中扮演重要角色.对猪链球菌2型89K毒力岛功能性基因的深入剖析有助于更全面地掌握病原菌的致病特性.综述了猪链球菌2型89K毒力岛的结构与进化过程,以及国内外对毒力岛中二元信号转导系统、Ⅳ型分泌系统、ABC转运蛋白、毒素-抗毒素系统等重要基因的研究进展,力图从基因水平为猪链球菌2型的致病机制寻找突破口.     

结核分枝杆菌信号转导与耐药的研究进展

摘要:结核分枝杆菌感染每年导致200万人口死亡,而化疗已经产生了严重的广泛传播的耐药性。信号转导系统是细菌适应周围环境变化的重要分子机制,是否介导细菌耐药性的产生,尚无清楚的认识。本文主要介绍了结核分枝杆菌的12对二元信号转导系统并分析了其与耐药性产生的关系。通过对近期研究的分析,我们发现MprB/A、PhoR/P、DosR/S/T、SenX3/RegX3、MtrB/A五对二元信号转导系统有可能通过不同的机制使结核分枝杆菌对抗结核药物发生耐药性,因此二元信号转导系统是有效的调控靶位点,有可能应用小分子化合物靶向调节二元信号转导途径以逆转耐药。     

植物抗病的信号转导途径

植物在遭受不同病原菌入侵时会表现出不同的反应,若病原菌具有逃避寄主的识别并破坏寄主防御系统的能力则表现感病;若植物能及时识别病原菌并激活自身的防御体系,将表现出抗病性,而特异性的抗病性常常伴有过敏反应的产生。那么植物对病原菌的最初识别,识别后的信号转导以及抗病性过程究竟是怎样的呢？本文将对这一问题进行概述。     

植物系统获得性抗性的信号转导

坏死病原菌（necrotizingpathogen）的侵染或者一些化学因子的处理能诱导植物的非侵染或非处理部位产生对多种病原再侵染产生抗性,即系统获得性抗性（systemicacquiredresistance,SAR）。获得系统抗性的组织中SAR基因产物的累积和防卫反应的潜在诱导增强（potentiation）是其两类抗病机制。SAR至少有通过水杨酸（salicylicacid,SA）或茉莉酸（jasmonicacid,JA）、乙烯（ethylene）为系统信号分子的两类信号转导途径。遗传分析已用于SAR产生的信号转导过程的分析,一些与SAR信号转导相关的基因已经和正在克隆,这些基因具有明显提高植物广谱抗性的潜能。     

枯草芽孢杆菌感受态研究新进展

在枯草芽孢杆菌中,感受态的形成受到一种二元信号转导系统的调节,这种系统对胞外的感受态信息素浓度作出感应而激活晚期感受态基因的表达。各种晚期感受态蛋白分别负责外源DNA的吸附、吸收和内源化,它们共同构成了DNA的运输系统。初步探讨了枯草芽孢杆菌感受态调节在细胞生长和进化中的意义。     

植物抗病防卫反应中的特异性钙信号

在植物细胞中,钙离子是普遍存在的第二信使,参与多种信号途径.大量研究表明,钙信使系统参与植物与病原菌互作的信号转导过程.近些年来,特异性钙信号在抗病中的作用越来越受到关注.文章综述了近年来在植物表达防卫反应过程中特异性钙信号的形式及其形成的生理机制的研究进展.     

鞘脂类与细胞信号传导的研究进展

当前生命科学研究中的一个中心问题是关于细胞代谢、生长、发育、适应、防御和凋亡等的调节机制,以及调控异常与疾病,特别是与一些重大疾病,如肿瘤、心血管病、糖尿病以及老年性痴呆等的关联.这些问题与生物信号分子所携带的信息的细胞内的传递有关.我们已经知道,细胞中存在着遣传信息传递系统,即由DNA(基因)转录成mRNA再翻译成蛋白质过程所形成的信息流,控制着生物体生长发育和新陈代谢.此外,细胞中还存在一个调节细胞代谢、生长、增殖、凋亡和各种功能活动的信号转导系统,它们由能接收信号的特定的受体、受体后的信号转导途径及其作用的终端所组成.它们能够对各种胞外信号分子,如激素、神经递质、细胞因子以及药物等起反应,通过细胞内的信号转导过程,调节代谢酶、离子通道、转录因子等的活性,产生各种生物效应.不同的信号转导通路间具有相互的联系和作用,形成复杂的网络.了解信号转导系统的组成及信号转导的机制,对于深入认识生命过程和揭示生命的本质具有重要意义,同时由于信号转导的失控可导致多种疫病,因此有关信号转导过程的研究还有助于阐明疾病的发生和发展的机制,并为新药的设计和发展新的治疗方法提供思路,达到预防和治疗疾病的目的.     

病原菌调节宿主细胞泛素化途径的研究进展

泛素化是真核生物特有的蛋白质翻译后修饰,广泛地参与宿主细胞各种信号通路和生理过程.病原菌常通过分泌毒性效应蛋白,对泛素和泛素结合酶进行独特的共价修饰,或者利用泛素连接酶和去泛素化酶的酶学活性,调节宿主泛素化过程,从而干扰宿主细胞的信号转导,促进细菌的感染和生存.本文概述了病原菌效应蛋白调节宿主泛素化途径的主要研究进展和最新发现.     

开启防御之门:植物抗病小体

NLR蛋白是存在于植物和动物中的一个免疫受体大家族,具有核苷酸结合域并富含亮氨酸重复序列。植物NLR通过识别病原菌特异效应子开启免疫信号转导。第1个植物NLR抗性蛋白于25年前克隆,但其激活机制仍不清楚,至今仍未获得一个完整的NLR蛋白结构。最近,柴继杰、周俭民和王宏伟实验室合作解析了第一个植物完整NLR ZAR1激活前后的结构,研究成果以两篇论文形式发表在"科学"杂志上,填补了NLR介导的免疫信号转导研究领域的空白。该文简要总结了相关研究进展,讨论了NLR免疫信号转导研究领域尚需解决的问题。     

Surface polysaccharides enable bacteria to evade plant immunity

Plants have an immune system to perceive pathogenic or potentially beneficial bacteria. Aspects of perception, signal transduction and the responses that the plant produces resemble features of innate immunity observed in animals. Plant reactions are various and include the production of antimicrobial compounds. Bacteria that are successful in establishing pathogenic or symbiotic interactions have developed multiple ways to protect themselves. We review the general importance of bacterial surface polysaccharides in the evasion of plant immune responses and elaborate on their role in protecting symbiotic bacteria against toxic reactive oxygen species during invasion of the host plant.     

Identification of a regulatory protein required for pressure-responsive gene expression in the deep-sea bacterium Photobacterium species strain SS9

Here, we report the characterization of a gene necessary for hydrostatic pressure regulation of gene expression in the deep-sea bacterium Photobacterium species strain SS9. The deduced amino acid sequence of the gene product shares extensive similarity to ToxR, a transmembrane DNA-binding protein first discovered as a virulence determinant in the pathogenic bacterium Vibrio cholerae . Changes in hydrostatic pressure induce changes in both the abundance and the activity of the SS9 ToxR protein (or the activity of a ToxR-regulated protein). As with other high-pressure-inducible phenomena observed in higher organisms, anaesthetics antagonize high-pressure signalling mediated by ToxR. It is suggested that SS9 ToxR has evolved the ability to respond to pressure-mediated alterations in membrane structure. V. cholerae and SS9 also share similarity in a ToxR-regulated protein, indicating that part of the ToxR regulon is conserved in diverse members of the family Vibrionaceae. The SS9 ToxR system represents a useful model for studies of signal transduction and environmental adaptation in the largest portion of the biosphere, the deep sea.     

Function and evolution of ubiquitous bacterial signaling adapter phosphopeptide recognition domain FHA

Forkhead-associated domain (FHA) is a phosphopeptide recognition domain embedded in some regulatory proteins. With similar fold type to important eukaryotic signaling molecules such as Smad2 and IRF3, the role of bacterial FHA domain is intensively pursued. Reported bacterial FHA domain roles include: regulation of glutamate and lipids production, regulation of cell shape, type III secretion, ethambutol resistance, sporulation, signal transduction, carbohydrate storage and transport, and pathogenic and symbiotic host–bacterium interactions. To provide basis for the studies of other bacterial FHA domain containing proteins, the status of bacterial FHA functionality and evolution were summarized.     

Protein Clusters in Phosphotyrosine Signal Transduction

Signal transduction systems based on tyrosine phosphorylation are central to cell–cell communication in multicellular organisms. Typically, in such a system, the signal is initiated by activating tyrosine kinases associated with transmembrane receptors, which induces tyrosine phosphorylation of the receptor and/or associated proteins. The phosphorylated tyrosines then serve as docking sites for the binding of various downstream effector proteins. It has long been observed that the cooperative association of the receptors and effectors produces higher-order protein assemblies (clusters) following signal activation in virtually all phosphotyrosine signal transduction systems. However, mechanistic studies on how such clustering processes affect signal transduction outcomes have only emerged recently. Here we review current progress in decoding the biophysical consequences of clustering on the behavior of the system, and how clustering affects how these receptors process information.     

Bacterial FHA domains: neglected players in the phospho-threonine signalling game?

Forkhead-associated (FHA) domains bind phospho-threonine peptides and are known to mediate phosphorylation-dependent protein–protein interactions in a variety of eukaryotic settings. However, their role in bacterial physiology and signalling has been largely neglected. We have surveyed bacterial FHA domains and discovered that they are implicated in many bacterial processes, including regulation of cell shape, type III secretion, sporulation, pathogenic and symbiotic host–bacterium interactions, carbohydrate storage and transport, signal transduction and ethambutol resistance. The way is now open to identify the targets of each FHA domain, and their roles in cellular physiology, and perhaps even to develop novel FHA-blocking antibacterial agents.     

Component of the Rhodospirillum centenum photosensory apparatus with structural and functional similarity to methyl-accepting chemotaxis protein chemoreceptors

Photosynthetic bacteria respond to alterations in light conditions by migrating to locations that allows optimal use of light as an energy source. Studies have indicated that photosynthesis-driven electron transport functions as an attractant signal for motility among purple photosynthetic bacteria. However, it is unclear just how the motility-based signal transduction system monitors electron flow through photosynthesis-driven electron transport. Recently, we have demonstrated that the purple photosynthetic bacterium Rhodospirillum centenum is capable of rapidly moving swarm cell colonies toward infrared light as well as away from visible light. Light-driven colony motility of R. centenum has allowed us to perform genetic dissection of the signaling pathway that affects photosynthesis-driven motility. In this study, we have undertaken sequence and mutational analyses of one of the components of a signal transduction pathway, Ptr, which appears responsible for transmitting a signal from the photosynthesis-driven electron transport chain to the chemotaxis signal transduction cascade. Mutational analysis demonstrates that cells disrupted for ptr are defective in altering motility in response to light, as well as defective in light-dependent release of methanol. We present a model which proposes that Ptr senses the redox state of a component in the photosynthetic cyclic electron transport chain and that Ptr is responsible for transmitting a signal to the chemotaxis machinery to induce a photosynthesis-dependent motility response.     

Helicobacter pylori induces formation of stress fibers and membrane ruffles in AGS cells by rac activation

Helicobacter pylori induces signaling cascades leading to changes in cytoskeleton and an inflammatory response. Information on the morphological changes and cytoskeletal rearrangements induced by attachment of the bacterium is contradictory and signal transduction pathways are not well known. Since rho family of small GTPases is known to mediate cytoskeletal response to various extracellular stimuli, and is also involved in several other important signal transduction pathways, we have investigated the role of rac and cdc42 in H. pylori-induced cytoskeletal changes in cultured carcinoma AGS cells. AGS cells grown with serum expressed actin filaments in the form of short stress fibers and thin network at the edges, which were depolymerized by removal of serum. In serum-starved cells both type I and type II strains of H. pylori induced formation of actin filaments and lamellipodia-like structures. Microinjection of active rac induced similar changes, but injection of inactive rac prevented the effects of H. pylori, while active or inactive cdc42 did not have any significant effect. Cytoskeletal effects of H. pylori were inhibited by actinomycin D, but not completely by cycloheximide. These results indicate that rac activation is involved in signal transduction cascade leading to cytoskeletal reorganization induced by H. pylori and that gene activation and synthesis of new proteins is necessary in this process.     

Alternative dimerization of receptor tyrosine kinases with signal transduction through a cellular membrane

Receptor tyrosine kinases (RTKs) occupy a separate functional niche among membrane receptors, which is determined by the special features of mechanisms of the signal transduction through a cellular membrane. RTKs are involved in the regulation of development and homeostasis of all the tissues of a human organism, playing a central role in cell proliferation, differentiation, and adhesion. A necessary condition of the biochemical signal transduction through a plasmatic membrane is a ligand-dependent or a ligand-independent dimerization (and/or an oligomerization) of RTKs which is accompanied by conformational rearrangements of all the RTK domains, including the α-helical transmembrane segments. In this review, the main aspects of structure-function relationship for RTKs from various receptor subfamilies are briefly discussed. It is shown in the light of the recently obtained biophysical and biochemical data that functioning of RTK receptors is mediated not only by protein–protein interactions, but by the state of the lipid environment as one of the main components of a self-consistent signal transduction system as well. The new principles of intercellular signal transduction through a membrane replenish the molecular mechanisms of the RTK functioning that have been earlier proposed and explain a number of paradoxes which are observed upon activation of wild-type receptors and the receptors with pathogenic transmembrane mutations. Understanding of the complex mechanisms of the signaling processes can facilitate the successful search for new opportunities of influence on the RTK biological functions with potential therapeutic consequences.     

Signal transduction pathways in Synechocystis sp. PCC 6803 and biotechnological implications under abiotic stress

Cyanobacteria have developed various response mechanisms in long evolution to sense and adapt to external or internal changes under abiotic stresses. The signal transduction system of a model cyanobacterium Synechocystis sp. PCC 6803 includes mainly two-component signal transduction systems of eukaryotic-type serine/threonine kinases (STKs), on which most have been investigated at present. These two-component systems play a major role in regulating cell activities in cyanobacteria. More and more co-regulation and crosstalk regulations among signal transduction systems had been discovered due to increasing experimental data, and they are of great importance in corresponding to abiotic stresses. However, mechanisms of their functions remain unknown. Nevertheless, the two signal transduction systems function as an integral network for adaption in different abiotic stresses. This review summarizes available knowledge on the signal transduction network in Synechocystis sp. PCC 6803 and biotechnological implications under various stresses, with focuses on the co-regulation and crosstalk regulations among various stress-responding signal transduction systems.