Disease relevance of GOLGB1

• GCP/IL-8-induced edema formation was found to be neutrophil dependent [1].
• Response to infliximab treatment in Crohn's disease is not associated with mutations in the CARD15 (NOD2) gene: an analysis in 534 patients from two multicenter, prospective GCP-level trials [2].
• The ICH GCP principles are discussed below within the framework of this recent typhoid fever vaccine study experience [3].
• The data suggest that GCP II inhibition may provide a meaningful and effective approach to the treatment of painful diabetic neuropathy [4].
• A woman aged 59 years with adult-onset progressive myopathy had anti-Golgi (giantin) autoantibody in the serum [5].

Psychiatry related information on GOLGB1

• Interestingly, even at relatively high doses of compounds, GCP II inhibition did not appear to be associated with learning/memory deficits in animals [6].

High impact information on GOLGB1

• GCP-WD depletion also blocks mitotic chromatin-mediated microtubule nucleation, resulting in failure of spindle assembly [7].
• Expression of cPLA(2) results in dispersion of giantin and beta-COP from their normal, condensed Golgi localization, and in marked disruption of the Golgi cisternae. cPLA(2) is present in Golgi fractions from noninfected LLC-PK(1) cells and rat kidney cortex [8].
• The acidic COOH-terminal domain of p115 links the Golgins, Giantin on COPI vesicles, to GM130 on Golgi membranes [9].
• Giantin, GM130, and GalNAcT2 relocated with approximately equal kinetics [10].
• In contrast, neither reduction of giantin below detectable levels, nor inhibition of p115 binding to GM130, had any detectable effect on Golgi structure or Golgi reassembly after cell division or brefeldin A washout [11].

Biological context of GOLGB1

• Molecular genetic analyses of a 376-kilodalton Golgi complex membrane protein (giantin) [12].
• Taken together, these results suggest that GCP60 is involved in the maintenance of the Golgi structure by interacting with giantin, affecting protein transport between the endoplasmic reticulum and the Golgi [13].
• To explain this result, we mapped the giantin binding site in p115 and found that it is located at the C-terminal acidic domain, the same domain involved in binding GM130 [14].
• Search for the protein sequence data base revealed that GCP364 has 75% identity in amino acid sequence with human GCP372/giantin, indicating that it is a rat homolog of the latter [15].
• Cumulative lod scores suggest that EDMD is approximately 2 cM from DXS52 (lod = 15.67) and very close to the factor VIII (F8C) and the red/green color pigment (R/GCP) loci, with respective lod scores of 9.62 and 10.77, without a single recombinant [16].

Anatomical context of GOLGB1

• The Golgi localization of giantin was not affected by the deletion of its CMD or by substitution with the CMD of syntaxin-2, a plasma membrane protein [17].
• The stable association of giantin with the putative released Golgi complex may contribute to its preferential autoantigenicity [18].
• Giantin exhibited reduced mobility on nonreducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis, was recovered in membrane fractions after differential centrifugation or sucrose flotation, and was not released from membranes by carbonate extraction [19].
• By forming a molecular tether between two membranes, p115, giantin, and GM130 may mediate multiple Golgi-related processes including vesicle transport, cisternae formation, and cisternal stacking [14].
• In the presence of a vasodilator substance, pmol amounts of GCP/IL-8 induced neutrophil accumulation that was fast in onset, relatively short of duration (half life 60 to 70 minutes), and was associated with a parallel time course of plasma protein extravasation [1].

Associations of GOLGB1 with chemical compounds

• Giantin is a resident Golgi protein that has an extremely long cytoplasmic domain (about 370 kDa) and is anchored to the Golgi membrane by the COOH-terminal membrane-anchoring domain (CMD) with no luminal extension [17].
• Herein, we show that it is in fact a Golgi protein with a C-terminal TMD and shares with giantin and golgin-84 a conserved histidine in its TMD [20].
• Golgi residents, such as TGN46, beta1,4-galactosyltransferase, giantin, and GM130, are still segregated and partitioned correctly into smaller stacked fragments in manganese-treated cells [21].
• Ocrl was localized to endosomes and Golgi membranes along with clathrin, giantin, the mannose 6-phosphate receptor, transferrin, and the early endosomal antigen 1 endosomal marker in fixed cells [22].
• GCP gels were bioadhesive but less so than hydroxypropylmethylcellulose, Carbopol 974NF (7:3) tablets [23].

Physical interactions of GOLGB1

• These results question a simple tethering model involving a ternary giantin-p115-GM130 complex and suggest that p115-giantin and p115-GM130 interactions might mediate independent membrane tethering events [14].

Co-localisations of GOLGB1

• Immunofluorescence and immunoelectron microscopy confirmed that GCP60 was co-localized with giantin in the Golgi complex [13].

Other interactions of GOLGB1

• GM130 and giantin have been shown to function in the p115-mediated docking of vesicles with Golgi cisternae [12] [24].
• CASP, the alternatively spliced product of the gene encoding the CCAAT-displacement protein transcription factor, is a Golgi membrane protein related to giantin [20].
• We also examined two other Golgi-resident proteins, golgin-84 and syntaxin-5, with a similar membrane topology as giantin [17].
• Autoantibodies to giantin, the largest Golgi autoantigen, were the predominant AGAs, being found in 50% of the AGA sera [18].
• Identification and characterization of a novel Golgi protein, GCP60, that interacts with the integral membrane protein giantin [13].

Analytical, diagnostic and therapeutic context of GOLGB1

• Epitope mapping of giantin was performed using six recombinant fragments spanning the entire protein [18].
• We have identified a 400-kDa protein, giantin, that is localized to the Golgi complex because its staining in double immunofluorescence experiments was coincident with that of galactosyltransferase, both in untreated cells and in cells treated with agents that disrupt Golgi structure [19].
• The patients were recruited from independent multicenter trials conducted according to GCP [2].
• 2. The implementation of GCP guidelines has not been fully satisfactory and clinical trials in Japan still run into problems [25].
• GCP gels could be loaded with up to 27.5% (w/w) of FITC-dextran by freeze-drying a dispersion of GCP in a solution of FITC-dextran [23].

References