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Biochimica Et Biophysica Acta Jan 2013
Topics: Animals; Endoplasmic Reticulum; Humans; Immunity, Innate; Kinetics; Mitochondria; Mitochondrial Dynamics; Proteolysis; Review Literature as Topic
PubMed: 23142418
DOI: 10.1016/j.bbamcr.2012.11.001 -
Traffic (Copenhagen, Denmark) Oct 2015Protein translocation into the endoplasmic reticulum (ER) constitutes the first step of protein secretion. ER protein import is essential in all eukaryotic cells and is... (Review)
Review
Protein translocation into the endoplasmic reticulum (ER) constitutes the first step of protein secretion. ER protein import is essential in all eukaryotic cells and is particularly critical in fast-growing tumour cells. Thus, the process can serve as target both for potential cancer drugs and for bacterial virulence factors. Inhibitors of protein transport across the ER membrane range from broad-spectrum to highly substrate-specific and can interfere with virtually any stage of this multistep process, and even with transport of endocytosed antigens into the cytosol for cross-presentation.
Topics: Animals; Antineoplastic Agents; Cytosol; Endoplasmic Reticulum; Humans; Membrane Transport Proteins; Protein Transport
PubMed: 26122014
DOI: 10.1111/tra.12308 -
Journal of Molecular Biology Aug 2016Glycosylation is a ubiquitous modification that occurs on proteins and lipids in all living cells. Consistent with their high complexity, glycans play crucial biological... (Review)
Review
Glycosylation is a ubiquitous modification that occurs on proteins and lipids in all living cells. Consistent with their high complexity, glycans play crucial biological roles in protein quality control and recognition events. Asparagine-linked protein N-glycosylation, the most complex glycosylation, initiates in the endoplasmic reticulum and matures in the Golgi apparatus. This process not only requires an accurate distribution of processing machineries, such as glycosyltransferases, glycosidases, and nucleotide sugar transporters, but also needs an efficient and well-organized factory that is responsible for the fidelity and quality control of sugar chain processing. In addition, accurate glycosylation must occur in coordination with protein trafficking and sorting. These activities are carried out by the Golgi apparatus, a membrane organelle in the center of the secretory pathway. To accomplish these tasks, the Golgi has developed into a unique stacked structure of closely aligned, flattened cisternae in which Golgi enzymes reside; in mammalian cells, dozens of Golgi stacks are often laterally linked into a ribbon-like structure. Here, we review our current knowledge of how the Golgi structure is formed and why its formation is required for accurate glycosylation, with the focus on how the Golgi stacking factors GRASP55 and GRASP65 generate the Golgi structure and how the conserved oligomeric Golgi complex maintains Golgi enzymes in different Golgi subcompartments by retrograde protein trafficking.
Topics: Animals; Biological Transport; Endoplasmic Reticulum; Glycosylation; Golgi Apparatus; Humans; Membrane Proteins; Protein Transport
PubMed: 26956395
DOI: 10.1016/j.jmb.2016.02.030 -
FEBS Letters Apr 2006Several biochemical reactions and processes of cell biology are compartmentalized in the endoplasmic reticulum (ER). The view that the ER membrane is basically a... (Review)
Review
Several biochemical reactions and processes of cell biology are compartmentalized in the endoplasmic reticulum (ER). The view that the ER membrane is basically a scaffold for ER proteins, which is permeable to small molecules, is inconsistent with recent findings. The luminal micro-environment is characteristically different from the cytosol; its protein and glutathione thiols are remarkably more oxidized, and it contains a separate pyridine nucleotide pool. The substrate specificity and activity of certain luminal enzymes are dependent on selective transport of possible substrates and co-factors from the cytosol. Abundant biochemical, pharmacological, clinical and genetic data indicate that the barrier function of the lipid bilayer and specific transport activities in the membrane make the ER a separate metabolic compartment.
Topics: Animals; Biological Transport; Cytosol; Endoplasmic Reticulum; Humans; Intracellular Membranes; Membrane Proteins
PubMed: 16580671
DOI: 10.1016/j.febslet.2006.03.050 -
The Biochemical Journal Aug 1992
Review
Topics: Amino Acid Sequence; Animals; Autoimmunity; Calcium; Calcium-Binding Proteins; Calreticulin; Chemical Phenomena; Chemistry, Physical; Endoplasmic Reticulum; Humans; Molecular Sequence Data; Tissue Distribution
PubMed: 1497605
DOI: 10.1042/bj2850681 -
The EMBO Journal Jan 2021The endoplasmic reticulum (ER) membrane protein complex (EMC) was identified over a decade ago in a genetic screen for ER protein homeostasis. The EMC inserts...
The endoplasmic reticulum (ER) membrane protein complex (EMC) was identified over a decade ago in a genetic screen for ER protein homeostasis. The EMC inserts transmembrane domains (TMDs) with limited hydrophobicity. Two recent cryo-EM structures, and a third model based on partial high- and low-resolution structures, suggest how this is accomplished.
Topics: Endoplasmic Reticulum; Humans; Intracellular Membranes; Membrane Proteins; Protein Biosynthesis; Protein Domains
PubMed: 33346928
DOI: 10.15252/embj.2020107407 -
American Journal of Respiratory and... Oct 2008
Topics: Apoptosis; Endoplasmic Reticulum; Humans; Oxidative Stress; Pulmonary Fibrosis
PubMed: 18832553
DOI: 10.1164/rccm.200807-1138ED -
Swiss Medical Weekly May 2002The endoplasmic reticulum represents the cell's quality control site for accurate folding of secretory and membrane proteins. Quality control is achieved through the... (Review)
Review
The endoplasmic reticulum represents the cell's quality control site for accurate folding of secretory and membrane proteins. Quality control is achieved through the association of ER chaperones with unfolded or misfolded polypeptide chains. In the ER stress response, upregulation of chaperones occurs as a consequence of misfolded proteins accumulating in the ER lumen; if these proteins fail to assume their native structure, they are retained in the ER and targeted for degradation by the proteasome. ER storage diseases (ERSDs) are a group of genetically based disorders in which mutant proteins fail to pass the ER quality control. Because all eukaryotic cells contain the ER, the clinical phenotype of ERSDs is very heterogeneous. Disease may result from the mere lack of the mutant protein in question and/or may be caused indirectly by toxic effects of the misfolded protein or aggregates thereof on the cell. Additionally, the cell's reaction to the ER stress may include signaling pathways which are ultimately detrimental. Experimentally, ERSDs serve as models to study the cellular reactions to a variety of perturbations. In particular, understanding the links between ER stress and cell degeneration may give valuable insights into the pathogenesis of other diseases where the accumulation of indigestible toxic material leads to cell injury.
Topics: Endoplasmic Reticulum; Humans; Metabolism, Inborn Errors; Protein Folding
PubMed: 12087487
DOI: 10.4414/smw.2002.09861 -
Biochimica Et Biophysica Acta Sep 2015The two major calcium (Ca²⁺) release channels on the sarco/endoplasmic reticulum (SR/ER) are inositol 1,4,5-trisphosphate and ryanodine receptors (IP3Rs and RyRs).... (Review)
Review
The two major calcium (Ca²⁺) release channels on the sarco/endoplasmic reticulum (SR/ER) are inositol 1,4,5-trisphosphate and ryanodine receptors (IP3Rs and RyRs). They play versatile roles in essential cell signaling processes, and abnormalities of these channels are associated with a variety of diseases. Structural information on IP3Rs and RyRs determined using multiple techniques including X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy and cryo-electron microscopy (EM), has significantly advanced our understanding of the mechanisms by which these Ca²⁺ release channels function under normal and pathophysiological circumstances. In this review, structural advances on the understanding of the mechanisms of IP3R and RyR function and dysfunction are summarized. This article is part of a Special Issue entitled: 13th European Symposium on Calcium.
Topics: Animals; Endoplasmic Reticulum; Humans; Inositol 1,4,5-Trisphosphate; Protein Structure, Tertiary; Ryanodine Receptor Calcium Release Channel; Structure-Activity Relationship
PubMed: 25461839
DOI: 10.1016/j.bbamcr.2014.11.023 -
Biological Research 2011Neurons are highly polarized, but the trafficking mechanisms that operate in these cells and the topological organization of their secretory organelles are still poorly... (Review)
Review
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.
Topics: Cell Membrane Permeability; Dendrites; Endoplasmic Reticulum; Humans; Membrane Proteins; Neuronal Plasticity; Protein Transport
PubMed: 21720677
DOI: 10.4067/S0716-97602011000100004