内质网膜形态维持的分子机制

内质网（endoplasmic reticulum,ER）是广泛存在于真核生物中的一类形态多样、功能重要的细胞器。内质网的连续膜系统由细胞核核膜、核周区域和外周区域组成。从形态上来看,内质网可以分为片状及管状两种结构,并且这两种形态又发挥着不同的生理功效。近年来的一些研究逐渐揭示了内质网这一复杂膜结构维持的机制,许多新发现的蛋白参与到内质网形态的维持过程中,其中整合膜蛋白reticulons和DP1/Yop1p既能诱导内质网管状结构的形成,又可能参与片状内质网的塑形,而atlastins和Sey1p则通过介导膜融合促进内质网管状网络的构建。更重要的是,一类称做遗传性痉挛性截瘫的人类神经退行性疾病与内质网形态的完整性有直接的关联。以近几年的研究结果为基础,对内质网膜形态的维持机制进行简要阐述。     

大鼠粒细胞内质网的电镜细胞化学反应

本实验用电镜细胞化学方法观察了大鼠骨髓粒细胞发育过程中内质网的髓过氧化物酶(MPO)反应和葡萄糖-6-磷酸酶(G-6-P)反??应。结果表明:MPO除定位于内质网、核膜,还出现在高尔基体和颗粒,它是粒细胞内质网的合成产物。G-6-P只在内质网、核膜中出现,它是内质网膜的结构成分。MPO反应的超微结构定位随粒细胞发育而变,利用这种变化作标志可以划分不同发育阶段的粒细胞;G-6-P反应定位不随发育而变,但反应强度与内质网的多寡、功能状态相对应。实验还表明核膜与内质网在结构、功能上的一致性;尤其在成熟粒细胞内质网很少的情况下,核膜可能代替了内质网的功能。     

内质网应激在肾脏疾病进展中的作用

内质网应激是机体对有害刺激的一种自身应答机制,细胞是存活还是死亡取决于刺激信号的强弱,适宜的内质网应激可保护细胞免受各种刺激的损害作用,而过强或过长时间的内质网应激使保护机制不能与损伤抗衡则扰乱内质网稳态,诱导细胞凋亡发生。内质网应激作为多种应激过程的共同通路,与多种肾脏疾病的进展密切相关,例如:肾小球疾病、肾小管间质损伤、肾缺血再灌注损伤、糖尿病肾病等。本文就内质网应激在肾脏疾病进展中作用的研究进展作一综述。     

内质网自噬的研究进展

内质网是蛋白、脂类、磷脂、类固醇以及寡糖的合成和修饰位点,同时也负责钙离子的储存与内源性及外源性产物的脱毒处理。与传统概念的巨自噬(macrophagy)不同,有一种自噬体对于其包含的物质是有高度选择性的,我们称它为选择性自噬。内质网自噬(ER-phagy)是调节内质网的碎片化,并把其递呈给溶酶体进行清除的一种选择性自噬的方式。它的主要功能是降解多余的内质网膜,控制内质网的体积和维持细胞稳态。内质网应激,营养枯竭,非折叠蛋白的聚集,病原入侵都能够导致内质网自噬。介导内质网自噬的受体包括FAM134B、SEC62、RTN3以及CCPG1。这些受体通过特异的模块把需要自噬处理的内质网与巨自噬相关分子联接。本文就内质网自噬受体的结构与功能以及内质网自噬在疾病中的作用进行概述,以期对这一新发现的选择性自噬的研究提供帮助。     

选择性内质网自噬受体研究进展

内质网自噬是一种可以清除受损内质网的选择性自噬,其主要功能是参与内质网容量和质量的控制,维持细胞稳态。选择性内质网自噬由相关的受体蛋白介导,这些蛋白在疾病发生发展中可能起到重要靶点效应。本文对选择性内质网自噬的作用及其与疾病的关系加以综述,并且归纳总结了相关受体蛋白介导内质网自噬的研究进展,以期对研究内质网自噬相关疾病的发生机制、发展过程及其防治手段提供新的思路和切入点。     

内质网应激与疾病

内质网是蛋白质合成与折叠、维持Ca²⁺动态平衡及合成脂类和固醇的场所。遗传或环境损伤引起内质网功能紊乱导致内质网应激,激活未折叠蛋白反应。未折叠蛋白反应是一种细胞自我保护性措施,但是内质网应激过强或持续时间过久可引起细胞凋亡。因此,内质网应激与众多人类疾病的发生发展密切相关。最近研究证明,癌症、炎症性疾病、代谢性疾病、骨质疏松症及神经退行性疾病等有内质网应激信号传递参与。然而内质网应激作为一个有效靶点参与各种疾病发挥作用的功能和机制仍然有待进一步研究。在近年来发表的文献基础上对内质网应激与疾病的关系,以及其可能的作用机制进行综述。     

内质网应激与肝脏疾病

内质网在细胞内分布广泛,是细胞内蛋白质、脂类和糖类合成的重要场所,是细胞内钙离子的储存场所,与物质运输、交换等作用密切相关。内质网稳态失衡会诱导内质网应激(Endoplasmic reticulum stress,ERS),持久应激会导致细胞凋亡。多项研究显示内质网应激与多种肝脏疾病密切相关。本文就内质网应激与肝脏疾病发病机制作一综述。     

植物内质网胁迫研究进展

内质网是蛋白质折叠和蛋白质糖基化修饰的重要场所。在内质网中存在多种调控机制来确保其中的蛋白质被正确地折叠、修饰和组装,以维持内质网稳态,这对于细胞正常的生理活动十分重要。然而,多种物理、化学因素均可使内质网稳态失衡,即在应激条件下,错误折叠和未折叠蛋白质的大量积累将导致内质网胁迫(endoplasmic reticulum stress, ERS),进而会引起未折叠蛋白质响应(unfolded protein response, UPR),极端情况下还会启动细胞程序性死亡(program cell death, PCD)。目前,植物内质网胁迫方面的研究较酵母和动物滞后,因此,从内质网质量控制系统和未折叠蛋白质响应2个方面对植物内质网胁迫现有研究进行了综述,以期为进一步理解内质网胁迫与植物逆境胁迫的关系提供参考。     

非酒精性脂肪性肝病细胞凋亡的内质网应激启动机制

内质网应激反应,是由于某些因素导致内质网的生理功能紊乱引起的一种细胞自我防御保护机制.内质网应激所诱导的细胞凋亡是近年来新被认识的一种凋亡途径,它不同于既往经典线粒体、死亡受体介导的细胞凋亡.当短暂性内质网应激时,通过激活未折叠蛋白反应来增强机体自我保护及生存能力;而持续性应激状态下,如非酒精性脂肪性肝病所诱导的内质网应激启动一系列凋亡途径如CHOP、JNK、Caspase等,上述凋亡途径可以加速诱导肝细胞凋亡,使NAFLD向肝纤维化方向甚至肝硬化发展.     

内质网相关细胞器互作的研究进展

真核细胞中内质网是由片状和管状两种不同形态组成的连续的生物膜结构,参与细胞内蛋白质和脂质的合成以及钙离子稳态的调控等。内质网通过蛋白-蛋白及蛋白-脂质的相互作用与多种膜性细胞结构建立膜接触位点,进行物质的交换、信号转导、膜动态性调控等生理活动。内质网与膜性细胞结构互作的缺陷也会引发许多人类重大疾病。该文介绍了内质网与一系列膜性细胞结构接触位点形成的分子机制及其潜在功能。     

Ca2+-homeostasis Differs Between Plant Species with Different Cold-tolerance at 4℃ Chilling

Electron microscopic observations revealed that the tissues of poplar (Populus deltoides Bartr. ex Marsh) apical bud cells, which were fixed by a modified procedure of potassium permanganate fixative, showed a distinct endomembrane organization, in particular, the structural associations of the endoplasmic reticulum (ER) with other membrane systems. The striking findings are that some ER elements were in connection with the nuclear envelopes of two adjacent cells through plasmodesmata, and many ER elements were also associated with mitochondria, plastids, Golgi bodies or the plasma membrane (PM), forming a bridge-like continuum among various endomembrane systems or between nucleus to nucleus. A great number of plasmodesmata existed between cells, indicating a perfectly integrated symplasmic structure in poplar apical bud meristem grown in a long day environment. During the short day-induced dormancy, ER contracted, leading to its disassociation between nuclei, and between the nucleus and organelles/plasmalemma in many cells. After dormancy broke and shoots growth resumed, contracted ER was no longer observed in the apical bud cells. The ER associations with other endomembrane systems and the intercellular communication channels were re-established similar to that of plants before dormancy induction. These observations suggest that ER may play an important role in linking-up between the nucleus and organelles, and between the nucleus and the nucleus (or cell-to-cell), and seemingly coordinating various physiological processes by the bridging-like associations. And the contraction of ER under short-day may result in the growth cessation and the development of dormancy in poplar.     

Cell-to-cell communication via plant endomembranes

Cell-to-cell communication was investigated in epidermal cells cut from stem internodal tissue of Nicotiana tabacum and Torenia fournieri. Fluorescently labelled peptides and dextrans were microinjected using iontophoresis into the cytoplasm andcortical endomembrane network of these cells. The microinjected endomembrane network was similar in location and structure to the endoplasmic reticulum (ER) as revealed by staining with 3, 3'-dihexyloxacarbocyanine iodide (DiOC(6)). No cell-to-cell movement of dextrans was observed following cytoplasmic injections but injection of dextrans into the endomembrane network resulted in rapid diffusion of the probes to neighbouring cells. It is proposed that the ER acts as a pathway for intercellular communication via the desmotubule through plasmodesmata.     

Alterations in ultrastructure and subcellular localization of Ca2+ in poplar apical bud cells during the induction of dormancy

In poplar (Populus deltoides Bartr. ex Marsh), bud dormancyand freezing tolerance were concomitantly induced by short-day(SD) photoperiods. Ultrastructural changes and the alterationin subcellular localization of calcium in apical bud cells associatedwith dormancy development were investigated. During the developmentof dormancy, the thickness of cell walls increased significantly,the number of starch granules increased, and there was a significantaccumulation of storage proteins in the vacuoles of the apicalbud cells. The most striking change was the constriction andblockage of the plasmodesmata. It was demonstrated that antimonate precipitation is a reliabletechnique for studying subcellular localization of calcium inpoplar apical bud cells. Under the long day (LD) photoperiod,electron-dense calcium antimonate precipitates were mainly localizedin vacuoles, intercellular spaces and plastids. Some antimonateprecipitates were also found in the cell walls and at the entranceof the plasmodesmata. However, there were few Ca²⁺ depositsfound in the cytosol and nucleus. After 20 d of SD exposure,when development of bud dormancy was initiated, calcium depositsin intercellular spaces were decreased, whereas some depositswere found in the cytosol and nuclei. From 28–49 d ofSD exposure, while dormancy was developing, a large number ofCa²⁺ precipitates were found in the cytosol and nuclei. Whendeep dormancy was reached after 77 d of SD exposure, Ca²⁺ depositsbecame fewer in both cytosol and nuclei, whereas numerous depositswere again observed in the cell walls and in the intercellularspaces. These results suggest that under the influence of SDphotoperiods, there are alterations in subcellular Ca²⁺ localization,and changes in ultrastructure of apical bud cells during thedevelopment of dormancy. The constriction and blockage of plasmodesmatamay cause the cessation of symplastic transport, limit cellularcommunication and signal transduction between adjacent cells,which in turn may lead to events associated with growth cessationand dormancy development in buds. Key words: Poplar, apical bud cells, Ca²⁺ subcellular localization, dormancy     

Behaviour of plasma membrane, cortical ER and plasmodesmata during plasmolysis of onion epidermal cells

During plasmolysis of onion epidermal cells, the contracting protoplast remains connected to the cell wall by an intricate, branched system of plasma membrane (PM) ‘Hechtian strands’ which stain strongly with the fluorescent probe DiOC₆. In addition, extensive regions of the cortical endoplasmic reticulum (ER) network remain anchored to the cell wall during plasmolysis and do not become incorporated into the contracting protoplast with the other cell organelles. These ER profiles become tightly encased by the PM as the latter contracts towards the centre of the cell. Thus, although the cortical ER is left outside the main protoplast body, it is nonetheless still bound by the PM of the cell. As well as being anchored to the wall, the cortical ER remains intimately linked with plasmodesmata and retains continuity between cells via the central desmotubules which become distended during plasmolysis. The PM also remains in close contact with the plasmodesmatal pore following plasmolysis. It is suggested that plasmodesmata, although sealed, may not be broken during plasmolysis, their substructure being preserved by continuity of both ER and PM through the plasmodesmatal pore. A structural model is presented which links the behaviour of PM, ER and plasmodesmata during plasmolysis.     

Plasmodesmal Dynamics in Both Woody Poplar and Herbaceous Winter Wheat Under Controlled Short Day and in Field Winter Period

Electron microscopic observation revealed that poplar (Populus deltoides Marsh.) and winter wheat (Triticum aestivum L. cv. Seward 80004) plasmodesmatal structures significantly changed under short day (SD, 8 h light) and in winter period, and such changes differed also noticeably between these two woody and herbaceous plants. Under long day (LD, 16 h light), many plasmodesmata with strong stain appeared in the cell wall of both poplar apical buds and winter wheat young leaf tissues, and connections of cytoplasmic endoplasmic reticulum (ER) with the ER in some plasmodesmata were observed. In addition, the typical “neck type” plasmodesmata were observed in winter wheat young leaf tissues, and their central desmotubules (appressed-ER) could be clearly identified. Under SD, many poplar plasmodesmata showed only a partial structure in the cell wall and appeared to be discontinued; some plasmodesmata swelled in the mid-wall, forming the cavity, and no appressed-ER appeared. In winter wheat, however, no noticeable alterations of plasmodesmata occurred, and the plasmodesmatal structure essentially remained same as it was under LD. In winter period, poplar plasmodesmata had a similar morphology as those observed under SD, however, winter wheat manifested at least two types of significant plasmodesmatal alterations: one plugged by electron-dense materials and the other of reduced neck region compared to those under LD. The above dynamic difference of the two species plasmodesmata under SD and winter period revealed the difference of their dormancy development under those environmental conditions.     

An ER‐peroxisome tether exerts peroxisome population control in yeast

Eukaryotic cells compartmentalize biochemical reactions into membrane‐enclosed organelles that must be faithfully propagated from one cell generation to the next. Transport and retention processes balance the partitioning of organelles between mother and daughter cells. Here we report the identification of an ER‐peroxisome tether that links peroxisomes to the ER and ensures peroxisome population control in the yeast Saccharomyces cerevisiae. The tether consists of the peroxisome biogenic protein, Pex3p, and the peroxisome inheritance factor, Inp1p. Inp1p bridges the two compartments by acting as a molecular hinge between ER‐bound Pex3p and peroxisomal Pex3p. Asymmetric peroxisome division leads to the formation of Inp1p‐containing anchored peroxisomes and Inp1p‐deficient mobile peroxisomes that segregate to the bud. While peroxisomes in mother cells are not released from tethering, de novo formation of tethers in the bud assists in the directionality of peroxisome transfer. Peroxisomes are thus stably maintained over generations of cells through their continued interaction with tethers.     

Chara tomentosa Antheridial Plasmodesmata at Various Stages of Spermatogenesis

Chara tomentosa antheridial plasmodesmata are described during proliferation and spermiogenesis. In antheridial filament cells which are cycling completely synchronously, unplugged plasmodesmata are filled with light cytoplasm. The same plasmodesmata are observed after cessation of mitotic division followed by the onset of synchronous spermiogenesis. Walls separating cells at different cell cycle stages and dividing antheridial filaments into asynchronous domains are plugged with a dense osmophilic substance. Similarly plugged plasmodesmata are present between antheridial cells of different types, e.g., capitular cells and antheridial filaments. In mid spermiogenesis when abundant endoplasmic reticulum (ER) appears temporarily it penetrates into plasmodesmata enabling cell-to-cell transport via ER cisternae. In late spermiogenesis there are no cisternae in plasmodesmata. This revised version was published online in July 2006 with corrections to the Cover Date.     

植物表达分泌蛋白的运输及定位

分泌途径主要由内膜系统构成,内质网和高尔基体对于分泌蛋白的运输及定位具有重要作用。分泌蛋白的运输包括顺行途径和逆行途径。蛋白质通过质流和受体介导的途径运输到小泡中。在植物中,分泌蛋白的运输主要通过小泡和相连的小管来完成。分子伴侣和质量控制不仅能优化新合成蛋白的折叠和组装,而且去除了有折叠缺陷的蛋白。分泌蛋白的定位需要特定的信号肽,而高尔基体固有蛋白以依赖跨膜长度的方式,沿着分泌途径的细胞器分布。本文对植物表达分泌蛋白的分泌途径及定位、相关的分子伴侣和质量控制进行了综述。     

The endoplasmic reticulum of plant cells and its role in protein maturation and biogenesis of oil bodies

The endoplasmic reticulum (ER) is the port of entry of proteins into the endomembrane system, and it is also involved in lipid biosynthesis and storage. This organelle contains a number of soluble and membrane-associated enzymes and molecular chaperones, which assist the folding and maturation of proteins and the deposition of lipid storage compounds. The regulation of translocation of proteins into the ER and their subsequent maturation within the organelle have been studied in detail in mammalian and yeast cells, and more recently also in plants. These studies showed that in general the functions of the ER in protein synthesis and maturation have been highly conserved between the different organisms. Yet, the ER of plants possesses some additional functions not found in mammalian and yeast cells. This compartment is involved in cell to cell communication via the plasmodesmata, and, in specialized cells, it serves as a storage site for proteins. The plant ER is also equipped with enzymes and structural proteins which are involved in the process of oil body biogenesis and lipid storage. In this review we discuss the components of the plant ER and their function in protein maturation and biogenesis of oil bodies. Due to the large number of cited papers, we were not able to cite all individual references and in many cases we refer the readers to reviews and references therein. We apologize to the authors whose references are not cited.