The carboxyl-terminal valine is required for transport of glycoprotein CD8 alpha from the endoplasmic reticulum to the intermediate compartment

There is evidence that a carboxyl-terminal valine residue is an anterograde transport signal for type I transmembrane proteins. Removal of the signal would either delay glycosylation in the Golgi complex of proteins destined to recycle to the endoplasmic reticulum or determine accumulation in the endoplasmic reticulum of newly synthesized proteins destined for the plasma membrane. We used the human CD8 alpha glycoprotein to investigate the role of the carboxyl-terminal valine in the exocytic pathway. Using immunofluorescence light microscopy, metabolic labeling, and cell fractionation, we demonstrate that removal of the carboxyl-terminal valine residue delays transport of CD8 alpha from the endoplasmic reticulum to the intermediate compartment. Removal of the residue did not affect the other steps of the exocytic pathway or the folding/dimerization and glycosylation processes. Therefore, it is likely that this signal plays a role in the transport of CD8 alpha from the endoplasmic reticulum to the intermediate compartment either before or during the formation of the transport vesicles that drive the exit the protein from the endoplasmic reticulum.     

ATF4在内质网应激调控成骨分化中的作用

为避免内质网中未折叠蛋白质的过度累积,真核细胞能激活一系列信号通路来维持内质网稳态,这个过程称为内质网应激。在骨生长发育中,适宜的内质网应激有助于成骨细胞、破骨细胞和软骨细胞的生长,可以促进骨髓间充质干细胞向成骨细胞分化。而过度的内质网应激会抑制成骨分化,严重的甚至导致骨质疏松、成骨不全等相关骨病的发生。内质网应激时可激活未折叠蛋白质反应,其主要是通过PERK/eIF2α/ATF4信号通路,上调转录激活因子4(ATF4)的表达。ATF4位于许多成骨分化调节因子的下游,是促进成骨分化的关键因子,在内质网应激对成骨分化的调节中发挥重要作用。在成骨分化过程中,适宜的内质网应激能通过激活PERK信号通路,诱导ATF4表达增加,进而上调骨钙素、骨涎蛋白等成骨所必需基因的表达,促进成骨分化。过度的内质网应激会激活ATF4/CHOP促凋亡途径,并导致Bax、胱天蛋白酶等凋亡信号分子的大量产生,进而导致细胞凋亡,抑制成骨分化。由于ATF4在ERS和成骨分化中的重要作用,ATF4在骨质疏松、成骨不全等骨相关疾病的治疗中具有重要意义。本文通过综述ATF4在内质网应激调控成骨分化中的作用机制,为相关骨性疾病治疗提供理论依据。     

ATF4在内质网应激调控成骨分化中的作用

为避免内质网中未折叠蛋白质的过度累积,真核细胞能激活一系列信号通路来维持内质网稳态,这个过程称为内质网应激。在骨生长发育中,适宜的内质网应激有助于成骨细胞、破骨细胞和软骨细胞的生长,可以促进骨髓间充质干细胞向成骨细胞分化。而过度的内质网应激会抑制成骨分化,严重的甚至导致骨质疏松、成骨不全等相关骨病的发生。内质网应激时可激活未折叠蛋白质反应,其主要是通过PERK/eIF2α/ATF4信号通路,上调转录激活因子4(ATF4)的表达。ATF4位于许多成骨分化调节因子的下游,是促进成骨分化的关键因子,在内质网应激对成骨分化的调节中发挥重要作用。在成骨分化过程中,适宜的内质网应激能通过激活PERK信号通路,诱导ATF4表达增加,进而上调骨钙素、骨涎蛋白等成骨所必需基因的表达,促进成骨分化。过度的内质网应激会激活ATF4/CHOP促凋亡途径,并导致Bax、胱天蛋白酶等凋亡信号分子的大量产生,进而导致细胞凋亡,抑制成骨分化。由于ATF4在ERS和成骨分化中的重要作用,ATF4在骨质疏松、成骨不全等骨相关疾病的治疗中具有重要意义。本文通过综述ATF4在内质网应激调控成骨分化中的作用机制,为相关骨性疾病治疗提供理论依据。     

The role of actin filaments in the organization of the endoplasmic reticulum in honeybee photoreceptor cells

Close to the bases of the photoreceptive microvilli, arthropod photoreceptors contain a dense network of endoplasmic reticulum that is involved in the regulation of the intracellular calcium concentration, and in the biogenesis of the photoreceptive membrane. Here, we examine the role of the cytoskeleton in organizing this submicrovillar endoplasmic reticulum in honeybee photoreceptors. Immunofluorescence microscopy of taxol-stabilized specimens, and electron-microscopic examination of high-pressure frozen, freeze-substituted retinae demonstrate that the submicrovillar cytoplasm lacks microtubules. The submicrovillar region contains a conspicuous F-actin system that codistributes with the submicrovillar endoplasmic reticulum. Incubation of retinal tissue with cytochalasin B leads to depolymerization of the submicrovillar F-actin system, and to disorganization and disintegration of the submicrovillar endoplasmic reticulum, indicating that an intact F-actin cytoskeleton is required to maintain the architecture of this domain of the endoplasmic reticulum. We have also developed a permeabilized cell model in order to study the physiological requirements for the interaction of the endoplasmic reticulum with actin filaments. The association of submicrovillar endoplasmic reticulum with actin filaments appears to be independent of ATP, Ca²⁺ and Mg²⁺, suggesting a tight static anchorage.     

Localization of the ethylene receptor ETR1 to the endoplasmic reticulum of Arabidopsis

The ethylene receptor ETR1 of Arabidopsis contains transmembrane domains responsible for ethylene binding and membrane localization. Sequence analysis does not provide information as to which membrane system of the plant cell ETR1 is localized. Examination by aqueous two-phase partitioning, sucrose density-gradient centrifugation, and immunoelectron microscopy indicates that ETR1 is predominantly localized to the endoplasmic reticulum. Localization of ETR1 showed no change following a cycloheximide chase. Ethylene binding by ETR1 did not affect localization to the endoplasmic reticulum, based upon analysis of plants treated with the ethylene precursor 1-aminocyclopropane- 1-carboxylic acid and by examination of a mutant receptor that does not bind ethylene. Determinants within the amino-terminal half of ETR1 are sufficient for targeting to and retention at the endoplasmic reticulum. These data support a central role of the plant endoplasmic reticulum in hormone perception and signal transduction.     

Effects of diabetes mellitus on salivary secretion and its composition in the human

Calreticulin is a Ca2+ binding/storage chaperone resident protein of the endoplasmic reticulum. This protein plays a key role in the calreticulin/calnexin cycle and the quality control pathways in the endoplasmic reticulum. Calreticulin deficiency is lethal due to impaired cardiac development. However, over-expression of the protein in developing and postnatal heart leads to bradycardia, complete heart block and sudden death. Ultrastructural evidence indicates that the deficiency associated with the absence of calreticulin in the heart may be due to a defect in the development of the contractile apparatus and/or a defect in development of the conductive system as well as a metabolic abnormality. Collectively, we postulate that calreticulin and endoplasmic reticulum plays an important role in cardiac development and postnatal pathologies.     

Localization of Ca2+ + Mg2+-ATPase of the sarcoplasmic reticulum in adult rat papillary muscle

Localization of the Ca2+ + Mg2+-ATPase of the sarcoplasmic reticulum in rat papillary muscle was determined by indirect immunofluorescence and immunoferritin labeling of cryostat and ultracryotomy sections, respectively. The Ca2+ + Mg2+-ATPase was found to be rather uniformly distributed in the free sarcoplasmic reticulum membrane but to be absent from both peripheral and interior junctional sarcoplasmic reticulum membrane, transverse tubules, sarcolemma, and mitochondria. This suggests that the Ca2+ + Mg2+-ATPase of the sarcoplasmic reticulum is antigenically unrelated to the Ca2+ + Mg2+-ATPase of the sarcolemma. These results are in agreement with the idea that the sites of interior and peripheral coupling between sarcoplasmic reticulum membrane and transverse tubules and between sarcoplasmic reticulum and sarcolemmal membranes play the same functional role in the excitation-contraction coupling in cardiac muscle.     

The effect of trifluoroperazine on the sarcoplasmic reticulum membrane

The inhibitory effect of trifluoroperazine (25-200 microM) on the sarcoplasmic reticulum calcium pump was studied in sarcoplasmic reticulum vesicles isolated from skeletal muscle. It was found that the lowest effective concentrations of trifluoroperazine (10 microM) displaces the Ca2+ dependence of sarcoplasmic reticulum ATPase to higher Ca2+ concentrations. Higher trifluoroperazine concentrations (100 microM) inhibit the enzyme even at saturating Ca2+. If trifluoroperazine is added to vesicles filled with calcium in the presence of ATP, inhibition of the catalytic cycle is accompanied by rapid release of accumulated calcium. ATPase inhibition and calcium release are produced by identical concentrations of trifluoroperazine and, most likely, by the same enzyme perturbation. These effects are related to partition of trifluoroperazine ino the sarcoplasmic reticulum membrane, and consequent alteration of the enzyme assembly within the membrane structure, and of the bilayer surface properties. The effect of trifluoroperazine was also studied on dissociated ('chemically skinned') cardiac cells undergoing phasic contractile activity which is totally dependent on calcium uptake and release by sarcoplasmic reticulum, and is not influenced by inhibitors of slow calcium channels. It was found that trifluoroperazine interferes with calcium transport by sarcoplasmic reticulum in situ, as well as with the role of sarcoplasmic reticulum in contractile activation.     

Location matters: the endoplasmic reticulum and protein trafficking in dendrites

Neurons are highly polarized, but the trafficking mechanisms that operate in these cells and the topological organization of their secretory organelles are still poorly understood. Particularly incipient is our knowledge of the role of the neuronal endoplasmic reticulum. Here we review the current understanding of the endoplasmic reticulum in neurons, its structure, composition, dendritic distribution and dynamics. We also focus on the trafficking of proteins through the dendritic endoplasmic reticulum, emphasizing the relevance of transport, retention, assembly of multi-subunit protein complexes and export. We additionally discuss the roles of the dendritic endoplasmic reticulum in synaptic plasticity.     

Paired cisternae of endoplasmic reticulum in developing ovarian oocytes of the golden hamster

Paired cisternae of rough endoplasmic reticulum linked together by two parallel structures exhibiting periodic striations have been observed in the cytoplasm of small pre-antrum oocytes in the golden hamster. They are present only in oocytes from animals older than 3 weeks of age. Two or more such pairs may be associated with one another, and similar structures have been observed in contact with the nuclear envelope. The peak incidence of the paired membranes coincides with a sharp increase in rough endoplasmic reticulum as the oocyte commences rapid growth. A suggested role for the paired membranes in production of new endoplasmic reticulum is discussed.     

The role of the endoplasmic reticulum in the accumulation of beta-amyloid peptide in Alzheimer's disease

Increased cerebral levels of Abeta(42) peptide, either as soluble or aggregated forms, are suggested to play a key role in the pathogenesis of Alzheimer's disease (AD). The identification of genetic defects in presenilins and beta-amyloid precursor protein (beta-APP) has led to the development of cellular and animal models that have helped in understanding aspects of the pathophysiology of the inherited early onset forms of AD. However, the majority of AD cases are sporadic with no clear or defined genetic basis. While genetic mutations are responsible for the accumulation of Abeta in early onset AD, the causative factors for accumulation of Abeta in the late onset AD forms are not known. This raises the possibility that Abeta accumulation in the absence of genetic mutations might result from abnormalities that indirectly affect Abeta production or its clearance. Currently, there is no consensus as to what are the mechanisms by which Abeta accumulates or as to which mechanisms underlie Abeta-induced neuronal death in AD. In this review, I will first describe the physiological role of endoplasmic reticulum in the cell and review some of the data supporting dysfunction of the endoplasmic reticulum as an early event leading to Abeta accumulation in familial AD. I will also discuss the possible role of oxidative stress and other factors as contributors in Abeta accumulation by reducing the clearance of Abeta from the endoplasmic reticulum. Finally, I will summarize data that show the endoplasmic reticulum stress as a mechanism underlying exogenous Abeta neurotoxicity.     

Redox regulation of glutenin subunit assembly in the plant endoplasmic reticulum

The glutenin fraction of wheat storage proteins consists of large polymers in which high‐ and low‐molecular‐weight subunits are connected by inter‐chain disulfide bonds. We found that assembly of a low‐molecular‐weight glutenin subunit in the endoplasmic reticulum is a rapid process that leads to accumulation of various oligomeric forms, and that this assembly is sensitive to perturbation of the cellular redox environment. In endoplasmic reticulum‐derived microsomes, low‐molecular‐weight glutenin subunits are subjected to hyper‐polymerization, indicating that cytosolic factors play an important role in limiting polymer size. Addition of physiological concentrations of reduced glutathione is sufficient to maintain the original polymerization pattern of the glutenin subunits upon cytosol dilution. Furthermore, we show that a low‐molecular‐weight glutenin subunit can be glutathionylated in endoplasmic reticulum‐derived microsomes, and that it can be directly reduced by glutathione in vitro. These results indicate that glutenin polymerization is sensitive to changes in the redox state of the cell, and suggest that the presence of a reducing cytosolic environment plays an important role in regulating disulfide bond formation in the endoplasmic reticulum of plant cells.     

The role of plastids and assimilate transport system in the control of plant development

Phylogenetic and ontogenetic relationships between the plastids, cell endoplasmic reticulum, and plant transport communication have been reviewed. The initiating role of plastids (endosymbionts) in the origin of endoplasmic reticulum (buffer zone of endosymbiogenesis) has been shown, as well as a similar role of endoplasmic reticulum in the development of transport communication of xylem and phloem. Plastids, sugars and transport system for their distribution can be interpreted as leading sections in the mechanism of developmental control: gene expression of nuclear genome and genome of organelles, cell and tissue differentiation, and plant morphogenesis. The conflict between the bulk of plant genome and low percentage of its realization is explained as a result of limitation of the nuclear genome realization by plastid genome. The concept of development as applied to plant ontogenesis has been critically analyzed. The possibilities of the concept correction by with the help of symbiogenetic hypothesis are discussed.     

内质网应激及线粒体功能障碍在糖尿病血管内皮损伤中作用的研究进展

血管内皮损伤是糖尿病血管并发症的起始环节,涉及多种机制,氧化应激被认为其中关键的环节,但补充外源性抗氧化剂的治疗目前仍存在争议。内质网及线粒体是参与细胞内活性氧生成的关键细胞器,探讨内质网应激、线粒体功能障碍及氧化应激之间的相互关系可能对于阐明糖尿病相关血管内皮功能障碍的发病机制有重要的意义。本文综述了近年关于内质网及线粒体功能障碍在糖尿病相关血管并发症中的研究进展并分析了二者的相互作用在氧化应激中的重要作用。     

Calreticulin, a multifunctional Ca2+ binding chaperone of the endoplasmic reticulum.

Calreticulin is a ubiquitous endoplasmic reticulum Ca2+ binding chaperone. The protein has been implicated in a variety of diverse functions. Calreticulin is a lectin-like chaperone and, together with calnexin, it plays an important role in quality control during protein synthesis, folding, and posttranslational modification. Calreticulin binds Ca2+ and affects cellular Ca2+ homeostasis. The protein increases the Ca2+ storage capacity of the endoplasmic reticulum and modulates the function of endoplasmic reticulum Ca2+-ATPase. Calreticulin also plays a role in the control of cell adhesion and steroid-sensitive gene expression. Recently, the protein has been identified and characterized in higher plants but its precise role in plant cells awaits further investigation.     

Calreticulin in the heart

Calreticulin is a Ca²⁺ binding/storage chaperone resident protein of the endoplasmic reticulum. This protein plays a key role in the calreticulin/calnexin cycle and the quality control pathways in the endoplasmic reticulum. Calreticulin deficiency is lethal due to impaired cardiac development. However, over-expression of the protein in developing and postnatal heart leads to bradycardia, complete heart block and sudden death. Ultrastructural evidence indicates that the deficiency associated with the absence of calreticulin in the heart may be due to a defect in the development of the contractile apparatus and/or a defect in development of the conductive system as well as a metabolic abnormality. Collectively, we postulate that calreticulin and endoplasmic reticulum plays an important role in cardiac development and postnatal pathologies. (Mol Cell Biochem 263: 137–142, 2004)     

Ultrasonography of the reticulum in 30 healthy Saanen goats

Background  

The reticulum plays a crucial role in the ruminant digestive tract because the primary cycle of rumen motility always starts with a reticular contraction. In contrast to cattle, there are only few results on the ultrasonographic examination of the reticulum in goats. Therefore, it was the goal of the present study, to describe the results of ultrasonography of the reticulum of 30 healthy Saanen goats.     

The role of creatine phosphokinase in supplying energy for the calcium pump system of heart sarcoplasmic reticulum.

An investigation of isolated and purified heart sarcoplasmic reticulum performed in the current study indicates the presence of significant creatine phosphokinase (CPK) activity in this preparation. The localization of CPK on the membrane of sarcoplasmic reticulum has been revealed also by an electron microscopic histochemical method. Under the conditions of the Ca(2+)-ATPase reaction in the presence of creatine phosphate, the release of creatine into the reaction medium is observed, the rate of the latter process being dependent on the MgATP concentration in accordance with the kinetic parameters of the Ca2+-ATPase reaction. CPK localized on the reticular membrane is able to maintain the high rate of calcium consumption by the sarcoplasmic reticulum vesicles. The results obtained demonstrate the close functional coupling between CPK and Ca2+-ATPase in the membrane of sarcoplasmic reticulum and indicate the important functional role of CPK in supplying energy for the Ca(2+)-ATPase reaction and ion transport across the membrane of heart sarcoplasmic reticulum.     

Studies on the development of the conducting tissue-system in the gametophytes of somePolytrichales

Summary An extensive system of endoplasmic reticulum is frequently encountered in the most highly developed leptoids at certain stages of their active life. This ER shows associations with the connections in end walls, and with certain other cell components. Its possible role in translocation is suggested.