scholarly journals Building of the Tetraspanin Web: Distinct Structural Domains of CD81 Function in Different Cellular Compartments

2006 ◽  
Vol 26 (4) ◽  
pp. 1373-1385 ◽  
Author(s):  
Tsipi Shoham ◽  
Ranjani Rajapaksa ◽  
Chiung-Chi Kuo ◽  
Joseph Haimovich ◽  
Shoshana Levy

ABSTRACT The tetraspanin web is composed of a network of tetraspanins and their partner proteins that facilitate cellular interactions and fusion events by an unknown mechanism. Our aim was to unravel the web partnership between the tetraspanin CD81 and CD19, a cell surface signaling molecule in B lymphocytes. We found that CD81 plays multiple roles in the processing, intracellular trafficking, and membrane functions of CD19. Surprisingly, these different roles are embodied in distinct CD81 domains, which function in the different cellular compartments: the N-terminal tail of CD81 has an effect on the glycosylation of CD19; the first transmembrane domain of CD81 is sufficient to support the exit of CD19 from the endoplasmic reticulum, although the large extracellular loop (LEL) of CD81 associates physically with CD19 early during biosynthesis; and finally, the TM2 and TM3 domains of CD81 play a role in the transmission of signals initiated upon engagement of the LEL. The participation of distinct CD81 domains in varied functions may explain the pleiotropic effects of CD81 within the tetraspanin web.

2008 ◽  
Vol 190 (14) ◽  
pp. 4865-4869 ◽  
Author(s):  
Matthew R. Spencer ◽  
Paul A. Beare ◽  
Iain L. Lamont

ABSTRACT Alternative sigma factor proteins enable transcription of specific sets of genes in bacterial cells. Their activities can be controlled by posttranslational mechanisms including inhibition by antisigma proteins and proteolytic degradation. PvdS is an alternative sigma factor that is required for expression of genes involved in synthesis of a siderophore, pyoverdine, by Pseudomonas aeruginosa. In the absence of pyoverdine, the activity of PvdS is inhibited by a membrane-spanning antisigma factor, FpvR. Inhibition is relieved by a cell surface signaling pathway. In this pathway, a combination of pyoverdine and a cell surface receptor protein, FpvA, suppresses the antisigma activity of FpvR, enabling transcription of PvdS-dependent genes. In this research, we investigated proteolytic degradation of PvdS in response to the signaling pathway. Proteolysis of PvdS was observed in strains of P. aeruginosa in which FpvR had anti-sigma factor activity due to the absence of pyoverdine or the FpvA receptor protein or overproduction of FpvR. Suppression of antisigma activity by addition of pyoverdine or through the absence of FpvR prevented detectable proteolysis of PvdS. The amounts of PvdS were less in bacteria in which proteolysis was observed, and reporter gene assays showed that this reduction was not due to decreased expression of PvdS. In wild-type bacteria, there was an average of 730 molecules of PvdS per cell in late exponential growth phase. Our results show that proteolysis and amounts of PvdS are affected by the antisigma factor FpvR and that this activity of FpvR is controlled by the cell surface signaling pathway.


2019 ◽  
Vol 316 (5) ◽  
pp. R525-R534 ◽  
Author(s):  
Zachary R. Shaheen ◽  
Benjamin S. Christmann ◽  
Joshua D. Stafford ◽  
Jason M. Moran ◽  
R. Mark L. Buller ◽  
...  

Double-stranded (ds) RNA, both synthetic and produced during virus replication, rapidly stimulates MAPK and NF-κB signaling that results in expression of the inflammatory genes inducible nitric oxide synthase, cyclooxygenase 2, and IL-1β by macrophages. Using biochemical and genetic approaches, we have identified the chemokine ligand-binding C-C chemokine receptor type 5 (CCR5) as a cell surface signaling receptor required for macrophage expression of inflammatory genes in response to dsRNA. Activation of macrophages by synthetic dsRNA does not require known dsRNA receptors, as poly(inosinic:cytidylic) acid [poly(I:C)] activates signaling pathways leading to expression of inflammatory genes to similar levels in wild-type and Toll-like receptor 3- or melanoma differentiation antigen 5-deficient macrophages. In contrast, macrophage activation in response to poly(I:C) is attenuated in macrophages isolated from mice lacking CCR5. These findings support a role for CCR5 as a cell surface signaling receptor that participates in activation of inflammatory genes in macrophages in response to the viral dsRNA mimetic poly(inosinic:cytidylic) acid by pathways that are distinct from classical dsRNA receptor-mediated responses.


2014 ◽  
Vol 29 (4) ◽  
pp. 431-435 ◽  
Author(s):  
Annat Raiter ◽  
Alexander Vilkin ◽  
Rachel Gingold ◽  
Zohar Levi ◽  
Marisa Halpern ◽  
...  

Background The identification of new biomarkers is required for early diagnosis of colorectal carcinoma patients (CRC), since about 20% of these patients are initially diagnosed with a distant metastatic disease. GRP78, a heat shock protein, functions also as a cell surface signaling receptor of cells under physiological stress. GRP78 was found to be expressed on the cell surface of various tumor cells. The presence of autoantibodies to GRP78 in cancer patient's serum was found to be correlated with a poor prognosis. In this study we aimed to identify anti-GRP78 antibodies in the serum of 85 patients diagnosed by colonoscopy, as an early detection biomarker. Methods We developed an ELISA assay with recombinant GRP78 immobilized on 96-well culture plates and used an anti-IgG antibody to measure the sole anti-GRP78 IgGs. Results Testing for anti-GRP78 showed a significant increase in antibody titer in patients with a polyp and in CRC patients (p<0.001) compared to healthy subjects. Conclusions This is the first study showing the presence of anti-GRP78 at the very early stages of CRC.


2017 ◽  
Author(s):  
Henry Heberle ◽  
Marcelo Falsarella Carazzolle ◽  
Guilherme P. Telles ◽  
Gabriela Vaz Meirelles ◽  
Rosane Minghim

AbstractBackgroundThe advent of “omics” science has brought new perspectives in contemporary biology through the high-throughput analyses of molecular interactions, providing new clues in protein/gene function and in the organization of biological pathways. Biomolecular interaction networks, or graphs, are simple abstract representations where the components of a cell (e.g. proteins, metabolites etc.) are represented by nodes and their interactions are represented by edges. An appropriate visualization of data is crucial for understanding such networks, since pathways are related to functions that occur in specific regions of the cell. The force-directed layout is an important and widely used technique to draw networks according to their topologies. Placing the networks into cellular compartments helps to quickly identify where network elements are located and, more specifically, concentrated. Currently, only a few tools provide the capability of visually organizing networks by cellular compartments. Most of them cannot handle large and dense networks. Even for small networks with hundreds of nodes the available tools are not able to reposition the network while the user is interacting, limiting the visual exploration capability.ResultsHere we propose CellNetVis, a web tool to easily display biological networks in a cell diagram employing a constrained force-directed layout algorithm. The tool is freely available and open-source. It was originally designed for networks generated by the Integrated Interactome System and can be used with networks from others databases, like InnateDB.ConclusionsCellNetVis has demonstrated to be applicable for dynamic investigation of complex networks over a consistent representation of a cell on the Web, with capabilities not matched elsewhere.


2021 ◽  
Vol 12 ◽  
Author(s):  
Dagmar Hromadová ◽  
Aleš Soukup ◽  
Edita Tylová

Responsiveness to environmental conditions and developmental plasticity of root systems are crucial determinants of plant fitness. These processes are interconnected at a cellular level with cell wall properties and cell surface signaling, which involve arabinogalactan proteins (AGPs) as essential components. AGPs are cell-wall localized glycoproteins, often GPI-anchored, which participate in root functions at many levels. They are involved in cell expansion and differentiation, regulation of root growth, interactions with other organisms, and environmental response. Due to the complexity of cell wall functional and regulatory networks, and despite the large amount of experimental data, the exact molecular mechanisms of AGP-action are still largely unknown. This dynamically evolving field of root biology is summarized in the present review.


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