Dataset Information

Molecular insights into vesicle tethering at the Golgi by the conserved oligomeric Golgi (COG) complex and the golgin TATA element modulatory factor (TMF).

ABSTRACT: Protein sorting between eukaryotic compartments requires vesicular transport, wherein tethering provides the first contact between vesicle and target membranes. Here we map and start to functionally analyze the interaction network of the conserved oligomeric Golgi (COG) complex that mediates retrograde tethering at the Golgi. The interactions of COG subunits with members of transport factor families assign the individual subunits as specific interaction hubs. Functional analysis of selected interactions suggests a mechanistic tethering model. We find that the COG complex interacts with two different Rabs in addition to each end of the golgin "TATA element modulatory factor" (TMF). This allows COG to potentially bridge the distance between the distal end of the golgin and the target membrane thereby promoting tighter docking. Concurrently we show that the central portion of TMF can bind to Golgi membranes that are liberated of their COPI cover. This latter interaction could serve to bring vesicle and target membranes into close apposition prior to fusion. A target selection mechanism, in which a hetero-oligomeric tethering factor organizes Rabs and coiled transport factors to enable protein sorting specificity, could be applicable to vesicle targeting throughout eukaryotic cells.

SUBMITTER: Miller VJ

PROVIDER: S-EPMC3567674 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Molecular insights into vesicle tethering at the Golgi by the conserved oligomeric Golgi (COG) complex and the golgin TATA element modulatory factor (TMF).

Miller Victoria J VJ Sharma Prateek P Kudlyk Tetyana A TA Frost Laura L Rofe Adam P AP Watson Irene J IJ Duden Rainer R Lowe Martin M Lupashin Vladimir V VV Ungar Daniel D

The Journal of biological chemistry 20121213 6

Protein sorting between eukaryotic compartments requires vesicular transport, wherein tethering provides the first contact between vesicle and target membranes. Here we map and start to functionally analyze the interaction network of the conserved oligomeric Golgi (COG) complex that mediates retrograde tethering at the Golgi. The interactions of COG subunits with members of transport factor families assign the individual subunits as specific interaction hubs. Functional analysis of selected inte ...[more]

PMID: 23239882

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Project description:BackgroundCortical folding is related to the functional organization of the brain. The TMF-1 regulated protein (TRNP1) regulates the expansion and folding of the mammalian cerebral cortex, a process that may have been accelerated by the domestication of dogs. The objectives of this study were to sequence the TRNP1 gene in dogs and related canid species, provide evidence of its expression in dog brain and compare the genetic variation within dogs and across the Canidae. The gene was located in silico to dog chromosome 2. The sequence was experimentally confirmed by amplifying and sequencing the TRNP1 exonic and promoter regions in 72 canids (36 purebred dogs, 20 Gy wolves and wolf-dog hybrids, 10 coyotes, 5 red foxes and 1 Gy fox).ResultsA partial TRNP1 transcript was isolated from several regions in the dog brain. Thirty genetic polymorphisms were found in the Canis sp. with 17 common to both dogs and wolves, and only one unique to dogs. Seven polymorphisms were observed only in coyotes. An additional 9 variants were seen in red foxes. Dogs were the least genetically diverse. Several polymorphisms in the promoter and 3'untranslated region were predicted to alter TRNP1 function by interfering with the binding of transcriptional repressors and miRNAs expressed in neural precursors. A c.259_264 deletion variant that encodes a polyalanine expansion was polymorphic in all species studied except for dogs. A stretch of 15 nucleotides that is found in other mammalian sequences (corresponding to 5 amino acids located between Pro58 and Ala59 in the putative dog protein) was absent from the TRNP1 sequences of all 5 canid species sequenced. Both of these aforementioned coding sequence variations were predicted to affect the formation of alpha helices in the disordered region of the TRNP1 protein.ConclusionsPotentially functionally important polymorphisms in the TRNP1 gene are found within and across various Canis species as well as the red fox, and unique differences in protein structure have evolved and been conserved in the Canidae compared to all other mammalian species.

Project description:BackgroundGolgin-97 is a tethering factor in the trans-Golgi network (TGN) and is crucial for vesicular trafficking and maintaining cell polarity. However, the significance of golgin-97 in human diseases such as cancer remains unclear.MethodsWe searched for a potential role of golgin-97 in cancers using Kaplan-Meier Plotter ( http://kmplot.com ) and Oncomine ( www.oncomine.org ) datasets. Specific functions of golgin-97 in migration and invasion were examined in golgin-97-knockdown and golgin-97-overexpressing cells. cDNA microarray, pathway analysis and qPCR were used to identify gene profiles regulated by golgin-97. The role of golgin-97 in NF-?B signaling pathway was examined by using subcellular fractionation, luciferase reporter assay, western blot analysis and immunofluorescence assay (IFA).ResultsWe found that low expression of golgin-97 correlated with poor overall survival of cancer patients and was associated with invasiveness in breast cancer cells. Golgin-97 knockdown promoted cell migration and invasion, whereas re-expression of golgin-97 restored the above phenotypes in breast cancer cells. Microarray and pathway analyses revealed that golgin-97 knockdown induced the expression of several invasion-promoting genes that were transcriptionally regulated by NF-?B p65. Mechanistically, golgin-97 knockdown significantly reduced I?B? protein levels and activated NF-?B, whereas neither I?B? levels nor NF-?B activity was changed in TGN46- or GCC185-knockdown cells. Conversely, golgin-97 overexpression suppressed NF-?B activity and restored the levels of I?B? in golgin-97-knockdown cells. Interestingly, the results of Golgi-disturbing agent treatment revealed that the loss of Golgi integrity was not involved in the NF-?B activation induced by golgin-97 knockdown. Moreover, both TGN-bound and cytosolic golgin-97 inhibited NF-?B activation, indicating that golgin-97 functions as an NF-?B suppressor regardless of its subcellular localization.ConclusionOur results collectively demonstrate a novel and suppressive role of golgin-97 in cancer invasiveness. We also provide a new avenue for exploring the relationship between the TGN, golgin-97 and NF-?B signaling in tumor progression.

Dataset Information

Molecular insights into vesicle tethering at the Golgi by the conserved oligomeric Golgi (COG) complex and the golgin TATA element modulatory factor (TMF).

Publications

Molecular insights into vesicle tethering at the Golgi by the conserved oligomeric Golgi (COG) complex and the golgin TATA element modulatory factor (TMF).

Similar Datasets

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