Search results for "Endoplasmic Reticulum"
showing 10 items of 306 documents
A closer look at the cholesterol sensor
2002
Abstract Transport of the sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP)–SREBP complex from the endoplasmic reticulum (ER) to the Golgi is the central event mediating the cholesterol-feedback process in mammalian cells. A conformational change in SCAP is a crucial step; when cholesterol levels are high, the conformation of SCAP enables the SCAP–SREBP complex to associate with an insulin-induced gene (INSIG) retention protein in the ER. By contrast, when cholesterol levels are low, SCAP switches to a conformation that enables the dissociation of the retention protein and the association of SCAP–SREBP with COP II vesicles.
Sorting signals in the cytosolic tail of membrane proteins involved in the interaction with plant ARF1 and coatomer.
2004
Summary In mammals and yeast, a cytosolic dilysine motif is critical for endoplasmic reticulum (ER) localization of type I membrane proteins. Retrograde transport of type I membrane proteins containing dilysine motifs at their cytoplasmic carboxy (C)-terminal tail involves the interaction of these motifs with the COPI coat. The C-terminal dilysine motif has also been shown to confer ER localization to type I membrane proteins in plant cells. Using in vitro binding assays, we have analyzed sorting motifs in the cytosolic tail of membrane proteins, which may be involved in the interaction with components of the COPI coat in plant cells. We show that a dilysine motif in the −3,−4 position (rel…
Multiple modes of cell death in neuroendocrine tumors induced by artesunate.
2020
Abstract Background The paucity of effective treatment in neuroendocrine tumors (NETs) encouraged us to investigate the therapeutic value of artesunate (ART) promised by its inhibitory effect against various tumors and broad safety profile. Methods We evaluated the impact of ART on three NET cell lines, BON-1, QGP-1 and NCI-H727 on cellular and molecular levels. Results Our results showed that ART induced endoplasmic reticulum (ER) stress through phosphorylation of eIF2α, which further gave rise to autophagy in all three NET cell lines. Specifically, apoptosis and ferroptosis were also observed in BON-1 cells, which made BON-1 cell line more vulnerable upon ART treatment. The different sens…
ER stress in human hepatic cells treated with Efavirenz: Mitochondria again
2013
Background & Aims ER stress is associated with a growing number of liver diseases, including drug-induced hepatotoxicity. The non-nucleoside analogue reverse transcriptase inhibitor Efavirenz, a cornerstone of the multidrug strategy employed to treat HIV1 infection, has been related to the development of various adverse events, including metabolic disturbances and hepatic toxicity, the mechanisms of which remain elusive. Recent evidence has pinpointed a specific mitochondrial effect of Efavirenz in human hepatic cells. This study assesses the induction of ER stress by Efavirenz in the same model and the implication of mitochondria in this process. Methods Primary human hepatocytes and Hep3B…
ER-to-Golgi Transport: The COPII-Pathway
2006
The endoplasmic reticulum (ER) is the starting site of the journey of newly synthesized proteinsto the apoplast, plasma membrane and to the vacuolar compartments. Transport between these membranecompartments of the secretory pathway in eukaryotic cells is mediated by vesicles, which are producedby a budding mechanism involving coat proteins that capture specific cargo molecules and helppackage them into coated vesicles. These vesicles are known as COPII-coated vesicles, and are usuallyisolated after their induction in vitro using microsomal membranes, cytosol and a non-hydrolyzableGTP-analogue. COPII-coated vesicles are formed at specific sites in the ER known as ER-exit sites(ERES). ERES a…
Impaired Transporter Associated with Antigen Processing (TAP) Function Attributable to a Single Amino Acid Alteration in the Peptide TAP Subunit TAP1
2003
Abstract The heterodimeric peptide transporter TAP belongs to the ABC transporter family. Sequence comparisons with the P-glycoprotein and cystic fibrosis transmembrane conductance regulator and the functional properties of selective amino acids in these ABC transporters postulated that the glutamic acid at position 263 and the phenylalanine at position 265 of the TAP1 subunit could affect peptide transporter function. To define the role of both amino acids, TAP1 mutants containing a deletion or a substitution to alanine at position 263 or 265 were generated and stably expressed in murine and human TAP1−/− cells. The different TAP1 mutants were characterized in terms of expression and funct…
TRAIL Triggers CRAC-Dependent Calcium Influx and Apoptosis through the Recruitment of Autophagy Proteins to Death-Inducing Signaling Complex
2021
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively kills various cancer cell types, but also leads to the activation of signaling pathways that favor resistance to cell death. Here, we investigated the as yet unknown roles of calcium signaling and autophagy regulatory proteins during TRAIL-induced cell death in leukemia cells. Taking advantage of the Gene Expression Profiling Interactive Analysis (GEPIA) project, we first found that leukemia patients present a unique TRAIL receptor gene expression pattern that may reflect their resistance to TRAIL. The exposure of NB4 acute promyelocytic leukemia cells to TRAIL induces intracellular Ca2+ influx through a calcium rel…
Expression and purification of polyhistidine-tagged rotavirus NSP4 proteins in insect cells
2003
The rotavirus nonstructural NSP4 protein, a transmembrane endoplasmic reticulum-specific glycoprotein, has been described as the first viral enterotoxin. Purified NSP4 or a peptide corresponding to NSP4 residues 114-135 induces diarrhea in young mice. NSP4 has a membrane-destabilizing activity and causes an increase in intracellular calcium levels and chloride secretion by a calcium-dependent signalling pathway in eucaryotic cells. In this study, four recombinant baculoviruses were generated expressing the rotavirus NSP4 glycoprotein from the human strains Wa and Ito, the porcine strain OSU, and the simian strain SA11, which belong to two different NSP4 genotypes, A and B. The recombinant g…
Hypusinated eIF5A is required for the translation of collagen
2021
AbstractThe evolutionary conserved elongation factor eIF5A is required for the translation of mRNAs that encode protein sequences with consecutive prolines or combined with glycine and charged amino acids. Mammalian collagens are enriched in putative eIF5A-dependent Pro-Gly-containing tripeptides. Here, we show that eIF5A is needed for heterologous expression of collagen in yeast, and using a dual luciferase reporter system we confirmed that eIF5A depletion interrupts translation at Pro-Gly-collagenic motifs. Using mouse fibroblasts, we showed that depletion of active eIF5A reduced collagen 1α (Col1a1) content, which became concentrated around the nuclei, in contrast to a stronger and all o…
Ovicide-induced serosa degeneration and its impact on embryonic development in Manduca sexta (Insecta: Lepidoptera)
2003
Abstract Eggs of Manduca sexta treated with the ovicide Ov. 165049 turn orange, and the embryos later die. The orange pigmentation is at first confined to the serosa, and is accompanied by pathological changes of serosal cells. Lipid vesicles aggregate and spindle-shaped electron-lucent vesicles—normally forming a single layer below the apical cell surface—greatly accumulate. The mitochondria swell considerably, and their matrices become electron-lucent. Subsequently, the serosal cells develop additional features of necrosis. They form many autophagic vacuoles which contain mostly degradating mitochondria, but also segregated rough endoplasmic reticulum (rER) and glycogen granules. The whol…