真核细胞伴侣素CCT及其与细胞骨架的关系

CCT(the chaperonin containing tailless complex polypeptide 1)是一种广泛存在于细胞浆中的异型寡聚蛋白,也是迄今为止真核细胞胞浆中发现的唯一伴侣素。目前认为大约15%的哺乳动物蛋白折叠需要CCT的参与,其中研究得最多的是肌动蛋白和微管蛋白。研究发现,CCT的异常会导致细胞骨架蛋白发生改变,甚至影响细胞骨架的形成与解聚。由此推测,一些细胞骨架相关疾病可能与CCT异常有关。     

肿瘤抑制蛋白APC的结构与功能

肿瘤抑制蛋白APC(adenomatous polyposis coli)是一种多功能蛋白,它不仅参与Wnt信号途径,调节β-链蛋白(β-catenin)的降解,同时也调节细胞骨架运动,影响细胞的迁移、黏合和分裂等。APC和其他相关因子之间的平衡对于肠上皮细胞的正常发育是十分重要的,这种平衡一旦被打破可能导致结肠功能的破坏及癌症的发生。该文着重介绍APC蛋白的结构及对细胞生长的影响。     

原生动物的细胞骨架蛋白及其功能组件

目前在原生动物中发现了许多新的细胞骨架蛋白,如中心元蛋白、副鞭毛杆蛋白等。深入研究发现,原生动物的细胞骨架在细胞的模式形成,细胞核的遗传中也具有重要作用。从功能组件角度着眼研究细胞骨架的功能,将有助于了解细胞骨架的进化机制。     

植物细胞骨架与细胞生长

文章就微管和肌动蛋白在植物细胞生长中的调节作用以及调节植物细胞骨架的信号途径的研究进展作简单介绍。     

细胞骨架对水通道蛋白2穿梭的影响

水通道蛋白2(aquaporin2,AQP2)作为肾脏最主要的水通道蛋白,由胞浆穿梭至管腔侧顶端膜上以增加集合管对水的通透性,从而增加肾脏对原尿中水的重吸收。AQP2的穿梭主要有赖于血管加压素的调节及其自身的磷酸化水平。最近越来越多的研究表明,细胞骨架在AQP2穿梭中发挥着重要的作用,本文将就这方面的文献进行总结。     

Rho蛋白和细胞骨架的关系

Rho蛋白作为细胞信号转导的分子开关之一,在细胞骨架动态变化中发挥着极其重要的作用。Rho蛋白对细胞骨架动态变化的调节是一个复杂的信号传递过程,涉及到Rho蛋白介导的信号通路中不同效应物间和Rho蛋白介导的多条信号通路间的相互作用。在Rho蛋白介导的信号通路中,上游调控因子、Rho蛋白、效应物在细胞中的正确定位对信号传递有着决定性的作用。     

植物激素与细胞骨架的排向

就植物微管和纤维素微纤丝在细胞骨架构成和延展中的作用、植物激素在微管和纤维素微纤丝排向中的调节功能作了介绍,并对细胞扩大和伸长的机制进行了分析和讨论.     

中国科学家在植物细胞骨架研究领域取得突破性进展

微管是细胞骨架的重要组成部分,为真核细胞生命活动所必需。与其它生物体类似,微管不仅在植物生长发育中起重要作用,而且参与响应外界环境信号。近期,中国科学家在解析植物微管精准切割及微管骨架动态重构调控机制的研究中取得突破性进展。     

细胞骨架--微管

《生物学通报》在2005年第2期第43页上介绍了“细胞骨架——肌动蛋白纤维”。除了微丝(microfilament)外,细胞骨架还包括微管(microtubule)和中间纤维(intemediate filament)。     

细胞骨架蛋白调节囊泡转运及其与神经疾病的关系

细胞内囊泡转运依赖于细胞骨架系统,细胞骨架为囊泡转运提供了轨道,而细胞骨架表面的马达蛋白则为其提供了动力。近年来,随着活细胞成像技术以及相关的生化、药理实验方法的不断进步,人们对囊泡转运的分子机制有了更加深入的认识。越来越多的实验结果表明,细胞骨架蛋白对囊泡转运有着重要的调节作用。囊泡转运的紊乱与多种神经疾病相关。囊泡转运分子调控机制的研究,将为多种神经疾病的治疗提供新的思路。     

APC nuclear membrane association and microtubule polarity

Background information. Directional cell migration is a fundamental feature of embryonic development, the inflammatory response and the metastatic spread of cancer. Migrating cells have a polarized morphology with an asymmetric distribution of signalling molecules and of the actin and microtubule cytoskeletons. The dynamic reorganization of the actin cytoskeleton provides the major driving force for migration in all mammalian cell types, but microtubules also play an important role in many cells, most notably neuronal precursors. Results. We previously showed, using primary fibroblasts and astrocytes in in vitro scratch‐induced migration assays, that the accumulation of APC (adenomatous polyposis coli; the APC tumour suppressor protein) at microtubule plus‐ends promotes their association with the plasma membrane at the leading edge. This is required for polarization of the microtubule cytoskeleton during directional migration. Here, we have examined the organization of microtubules in the soma of migrating neurons and fibroblasts. Conclusions. We find that APC, through a direct interaction with the NPC (nuclear pore complex) protein Nup153 (nucleoporin 153), promotes the association of microtubules with the nuclear membrane.     

结肠腺瘤性息肉病蛋白通过与SMAP/KAP3相互作用与微管结合

结肠腺瘤性息肉病基因(adenomatous polyposis coli,APC)的突变导致家族性结肠息肉腺瘤病和散发性结肠癌,APC基因编码一个具有多个结构域、多种磷酸化状态的大分子蛋白质.APC蛋白可通过C段直接或间接与微管结合,同时还可以通过中段与微管结合,但其结合的机制目前还不清楚.为进一步研究APC与其他蛋白质的相互作用,利用酵母双杂交技术运用APC中段（1 500 bp～4 800 bp）构建诱饵质粒,筛选人胎脑cDNA文库,得到一个与APC相互作用的蛋白SMAP/KAP3,SMAP/KAP3是驱动蛋白KIF3A/3B的相关蛋白.通过免疫共沉淀和双色免疫荧光共定位的方法,证实了APC与SMAP/KAP3在体内的相互作用,提示APC可能通过SMAP/KAP3-KIF3A/B参与沿微管的运动.     

Neuronal cytoskeleton in synaptic plasticity and regeneration

During development, dynamic changes in the axonal growth cone and dendrite are necessary for exploratory movements underlying initial axo‐dendritic contact and ultimately the formation of a functional synapse. In the adult central nervous system, an impressive degree of plasticity is retained through morphological and molecular rearrangements in the pre‐ and post‐synaptic compartments that underlie the strengthening or weakening of synaptic pathways. Plasticity is regulated by the interplay of permissive and inhibitory extracellular cues, which signal through receptors at the synapse to regulate the closure of critical periods of developmental plasticity as well as by acute changes in plasticity in response to experience and activity in the adult. The molecular underpinnings of synaptic plasticity are actively studied and it is clear that the cytoskeleton is a key substrate for many cues that affect plasticity. Many of the cues that restrict synaptic plasticity exhibit residual activity in the injured adult CNS and restrict regenerative growth by targeting the cytoskeleton. Here, we review some of the latest insights into how cytoskeletal remodeling affects neuronal plasticity and discuss how the cytoskeleton is being targeted in an effort to promote plasticity and repair following traumatic injury in the central nervous system.     

The Effect of cytoskeleton inhibitors on coccolith morphology in Coccolithus braarudii and Scyphosphaera apsteinii

The calcite platelets of coccolithophores (Haptophyta), the coccoliths, are among the most elaborate biomineral structures. How these unicellular algae accomplish the complex morphogenesis of coccoliths is still largely unknown. It has long been proposed that the cytoskeleton plays a central role in shaping the growing coccoliths. Previous studies have indicated that disruption of the microtubule network led to defects in coccolith morphogenesis in Emiliania huxleyi and Coccolithus braarudii. Disruption of the actin network also led to defects in coccolith morphology in E. huxleyi, but its impact on coccolith morphology in C. braarudii was unclear, as coccolith secretion was largely inhibited under the conditions used. A more detailed examination of the role of actin and microtubule networks is therefore required to address the wider role of the cytoskeleton in coccolith morphogenesis. In this study, we have examined coccolith morphology in C. braarudii and Scyphosphaera apsteinii following treatment with the microtubule inhibitors vinblastine and colchicine (S. apsteinii only) and the actin inhibitor cytochalasin B. We found that all cytoskeleton inhibitors induced coccolith malformations, strongly suggesting that both microtubules and actin filaments are instrumental in morphogenesis. By demonstrating the requirement for the microtubule and actin networks in coccolith morphogenesis in diverse species, our results suggest that both of these cytoskeletal elements are likely to play conserved roles in defining coccolith morphology.     

Microtubule cytoskeleton and morphogenesis in the amoebae of the myxomycete Physarum polycephalum

Summary— The amoebae of the myxomycete Physarum polycephalum are of interest in order to analyze the morphogenesis of the microtubule and microfilament cytoskeleton during cell cycle and flagellation. The amoebal interphase microtubule cytoskeleton consists of 2 distinct levels of organization, which correspond to different physiological roles. The first level is composed of the 2 kinetosomes or centrioles and their associated structures. The anterior and posterior kinetosomes forming the anterior and posterior flagella are morphologically distinguishable. Each centriole plays a role in the morphogenesis of its associated satellites and specific microtubule arrays. The 2 distinct centrioles correspond to the 2 successive maturation stages of the pro-centrioles which are built during prophase. The second level of organization consists of a prominent microtubule organizing center (mtoc 1) to which the anterior centriole is attached at least during interphase. This mtoc plays a role in the formation of the mitotic pole. These observations based on ultrastructural and physiological analyses of the amoebal cystoskeleton are now being extended to the biochemical level. The complex formed by the 2 centrioles and the mtoc 1 has been purified without modifying the microtubule-nucleating activity of the mtoc 1. Several microtubule-associated proteins have been characterized by their ability to bind taxol-stabilized microtubules. Their functions (e.g., microtubule assembly, protection of microtubules against dilution or cold treatment, phosphorylating and ATPase activities) are under investigation. These biochemical approaches could allow in vitro analysis of the morphogenesis of the amoebal microtubule cytoskeleton.     

Lipopolysaccharide induces distinct alterations in the microtubule cytoskeleton of monocytes

Microtubules are obligate functional elements of almost all eukaryotic cells. They are involved in a broad range of essential cellular functions and structural changes of this system may trigger cell death. Recently, we have reported that lipopolysaccharides inhibitin vitro microtubule formation due to exclusion of microtubule-associated proteins. The distinct epitopes of lipopolysaccharides responsible for these effects and thein vivo relevance of these data are unknown. Therefore, this study was conducted to elucidate the effects of lipid A, the biologically active motif of lipopolysaccharides, on microtubule formationin vitro and to prove whether lipopolysaccharides affect the microtubule architecture of cultured human monocytesin vivo. Despite a dose- and pH-dependent inhibition of microtubule formation by lipopolysaccharides, inhibition of microtubule assembly could be mimicked by lipid A. Near-infrared two-photon microscopy revealed that human peripheral blood monocytes accumulate lipopolysaccharides. A vesicular distribution pattern of lipopolysaccharides within the monocytes was observed. Confocal laser scanning microscopy demonstrated alterations in the microtubule architecture of monocytes after incubation with lipopolysaccharides. Lipid A seems to be responsible for the observed crosstalk between lipopolysaccharides and microtubule proteins. Furthermore, our data indicate that lipopolysaccharides may affect the microtubule architecture in human monocytes after intracellular accumulation directly. Therefore, we conclude, that the microtubule cytoskeleton is an essential intracellular target for sepsis-relevant bacterial components such as lipopolysaccharides. This revised version was published online in July 2006 with corrections to the Cover Date.     

Dynamic instabilities in the microtubule cytoskeleton: A state diagram

The dynamics of microtubule growth and disassembly is considered in the framework of the theory of nonequilibrium reaction-diffusion systems. The phase diagram contains regions corresponding to stable stationary and nonstationary solutions. Dynamic instabilities can arise from nonequilibrium kinetic transitions. Agents affecting the microtubule dynamics are classed into four types, and the interplay of their effects is analyzed.     

Building bridges: formin1 of Arabidopsis forms a connection between the cell wall and the actin cytoskeleton

Actin microfilament (MF) organization and remodelling is critical to cell function. The formin family of actin binding proteins are involved in nucleating MFs in Arabidopsis thaliana. They all contain formin homology domains in the intracellular, C‐terminal half of the protein that interacts with MFs. Formins in class I are usually targeted to the plasma membrane and this is true of Formin1 (AtFH1) of A. thaliana. In this study, we have investigated the extracellular domain of AtFH1 and we demonstrate that AtFH1 forms a bridge from the actin cytoskeleton, across the plasma membrane and is anchored within the cell wall. AtFH1 has a large, extracellular domain that is maintained by purifying selection and that contains four conserved regions, one of which is responsible for immobilising the protein. Protein anchoring within the cell wall is reduced in constructs that express truncations of the extracellular domain and in experiments in protoplasts without primary cell walls. The 18 amino acid proline‐rich extracellular domain that is responsible for AtFH1 anchoring has homology with cell‐wall extensins. We also have shown that anchoring of AtFH1 in the cell wall promotes actin bundling within the cell and that overexpression of AtFH1 has an inhibitory effect on organelle actin‐dependant dynamics. Thus, the AtFH1 bridge provides stable anchor points for the actin cytoskeleton and is probably a crucial component of the signalling response and actin‐remodelling mechanisms.