Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P11021 (BiP)
 2,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Morphological examination of the highly polarized protozoan parasite Toxoplasma gondii suggests that secretory traffic in this organism progresses from the endoplasmic reticulum to the Golgi apparatus using the nuclear envelope as an intermediate compartment. While the endoplasmic reticulum is predominantly located near the basal end of the parasite, the Golgi is invariably adjacent to the apical end of the nucleus, and the space between the Golgi and nuclear envelope is filled with numerous coatomer-coated vesicles. Staining with antiserum raised against recombinant T. gondii beta-COP confirms its association with the apical juxtanuclear region. Perturbation of protein secretion using brefeldin A, microtubule inhibitors or dithiothreitol disrupts the Golgi, causing swelling of the nuclear envelope, particularly at its basal end. Prolonged drug treatment leads to gross distention of the endoplasmic reticulum, filling the basal end of the parasite. Cloning and sequencing of the T. gondii homolog of the chaperonin protein BiP identifies the carboxy-terminal amino acid sequence HDEL as this organism's endoplasmic reticulum-retention signal. Appending the HDEL motif to a recombinant secretory protein (a chimera between the parasite's major surface protein fusion, P30, and the Green Fluorescent Protein) causes this secretory reporter to be retained intracellularly. P30-GFP-HDEL fluorescence was most intense within the nuclear envelope, particularly at the apical end. These data support a model of secretion in which protein traffic from the endoplasmic reticulum to Golgi occurs via the apical end of the nuclear envelope.
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PMID:The nuclear envelope serves as an intermediary between the ER and Golgi complex in the intracellular parasite Toxoplasma gondii. 1041 71

In some individuals with autosomal dominant isolated growth hormone deficiency, one copy of growth hormone lacks amino acids 32-71 and is severely misfolded. We transfected COS7 cells with either wild-type human growth hormone or Delta 32-71 growth hormone and investigated subcellular localization of growth hormone and other proteins. Delta 32-71 growth hormone was retained in the endoplasmic reticulum, whereas wild-type hormone accumulated in the Golgi apparatus. When cells transfected with wild-type or Delta 32-71 growth hormone were dually stained for growth hormone and the Golgi markers beta-COP, membrin or 58K, wild-type growth hormone was colocalized with the Golgi markers, but beta-COP, membrin and 58K immunoreactivity was highly dispersed or undetectable in cells expressing Delta 32-71 growth hormone. Examination of alpha-tubulin immunostaining showed that the cytoplasmic microtubular arrangement was normal in cells expressing wild-type growth hormone, but microtubule-organizing centers were absent in nearly all cells expressing Delta 32-71 growth hormone. To determine whether Delta 32-71 growth hormone would alter trafficking of a plasma membrane protein, we cotransfected the cells with the thyrotropin-releasing hormone (TRH) receptor and either wild-type or Delta 32-71 growth hormone. Cells expressing Delta 32-71 growth hormone, unlike those expressing wild-type growth hormone, failed to show normal TRH receptor localization or binding. Expression of Delta 32-71 growth hormone also disrupted the trafficking of two secretory proteins, prolactin and secreted alkaline phosphatase. Delta 32-71 growth hormone only weakly elicited the unfolded protein response as indicated by induction of BiP mRNA. Pharmacological induction of the unfolded protein response partially prevented deletion mutant-induced Golgi fragmentation and partially restored normal TRH receptor trafficking. The ability of some misfolded proteins to block endoplasmic reticulum-to-Golgi traffic may explain their toxic effects on host cells and suggests possible strategies for therapeutic interventions.
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PMID:Misfolded growth hormone causes fragmentation of the Golgi apparatus and disrupts endoplasmic reticulum-to-Golgi traffic. 1170 20

Mouse polyomavirus enters host cells internalized, similar to simian virus 40 (SV40), in smooth monopinocytic vesicles, the movement of which is associated with transient actin disorganization. The major capsid protein (VP1) of the incoming polyomavirus accumulates on membranes around the cell nucleus. Here we show that unlike SV40, mouse polyomavirus infection is not substantially inhibited by brefeldin A, and colocalization of VP1 with beta-COP during early stages of polyomavirus infection in mouse fibroblasts was observed only rarely. Thus, these viruses obviously use different traffic routes from the plasma membrane toward the cell nucleus. At approximately 3 h postinfection, a part of VP1 colocalized with the endoplasmic reticulum marker BiP, and a subpopulation of virus was found in perinuclear areas associated with Rab11 GTPase and colocalized with transferrin, a marker of recycling endosomes. Earlier postinfection, a minor subpopulation of virions was found to be associated with Rab5, known to be connected with early endosomes, but the cell entry of virus was slower than that of transferrin or cholera toxin B-fragment. Neither Rab7, a marker of late endosomes, nor LAMP-2 lysosomal glycoprotein was found to colocalize with polyomavirus. In situ hybridization with polyomavirus genome-specific fluorescent probes clearly demonstrated that, regardless of the multiplicity of infection, only a few virions delivered their genomic DNA into the cell nucleus, while the majority of viral genomes (and VP1) moved back from the proximity of the nucleus to the cytosol, apparently for their degradation.
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PMID:Mouse polyomavirus utilizes recycling endosomes for a traffic pathway independent of COPI vesicle transport. 1252 1

Toxin trafficking studies provide valuable information about endogenous pathways of intracellular transport. Subtilase cytotoxin (SubAB) is transported in a retrograde manner through the endosome to the Golgi and then to the endoplasmic reticulum (ER), where it specifically cleaves the ER chaperone BiP/GRP78 (Binding immunoglobin protein/Glucose-Regulated Protein of 78 kDa). To identify the SubAB Golgi trafficking route, we have used siRNA-mediated silencing and immunofluorescence microscopy in HeLa and Vero cells. Knockdown (KD) of subunits of the conserved oligomeric Golgi (COG) complex significantly delays SubAB cytotoxicity and blocks SubAB trafficking to the cis Golgi. Depletion of Rab6 and beta-COP proteins causes a similar delay in SubAB-mediated GRP78 cleavage and did not augment the trafficking block observed in COG KD cells, indicating that all three Golgi factors operate on the same 'fast' retrograde trafficking pathway. SubAB trafficking is completely blocked in cells deficient in the Golgi SNARE Syntaxin 5 and does not require the activity of endosomal sorting nexins SNX1 and SNX2. Surprisingly, depletion of Golgi tethers p115 and golgin-84 that regulates two previously described coat protein I (COPI) vesicle-mediated pathways did not interfere with SubAB trafficking, indicating that SubAB is exploiting a novel COG/Rab6/COPI-dependent retrograde trafficking pathway.
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PMID:The COG complex, Rab6 and COPI define a novel Golgi retrograde trafficking pathway that is exploited by SubAB toxin. 1967 99