Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Interaction of the α7-nicotinic subunit with its human-specific duplicated dupα7 isoform in mammalian cells: Relevance in human inflammatory responses.
Maldifassi MC
,
Martín-Sánchez C
,
Atienza G
,
Cedillo JL
,
Arnalich F
,
Bordas A
,
Zafra F
,
Giménez C
,
Extremera M
,
Renart J
,
Montiel C
.
???displayArticle.abstract???
The α7 nicotinic receptor subunit and its partially duplicated human-specific dupα7 isoform are coexpressed in neuronal and non-neuronal cells. In these cells, α7 subunits form homopentameric α7 nicotinic acetylcholine receptors (α7-nAChRs) implicated in numerous pathologies. In immune cells, α7-nAChRs are essential for vagal control of inflammatory response in sepsis. Recent studies show that the dupα7 subunit is a dominant-negative regulator of α7-nAChR activity in Xenopus oocytes. However, its biological significance in mammalian cells, particularly immune cells, remains unexplored, as the duplicated form is indistinguishable from the original subunit in standard tests. Here, using immunocytochemistry, confocal microscopy, coimmunoprecipitation, FRET, flow cytometry, and ELISA, we addressed this challenge in GH4C1 rat pituitary cells and RAW264.7 murine macrophages transfected with epitope- and fluorescent protein-tagged α7 or dupα7. We used quantitative RT-PCR of dupα7 gene expression levels in peripheral blood mononuclear cells (PBMCs) from patients with sepsis to analyze its relationship with PBMC α7 mRNA levels and with serum concentrations of inflammatory markers. We found that a physical interaction between dupα7 and α7 subunits in both cell lines generates heteromeric nAChRs that remain mainly trapped in the endoplasmic reticulum. The dupα7 sequestration of α7 subunits reduced membrane expression of functional α7-nAChRs, attenuating their anti-inflammatory capacity in lipopolysaccharide-stimulated macrophages. Moreover, the PBMC's dupα7 levels correlated inversely with their α7 levels and directly with the magnitude of the patients' inflammatory state. These results indicate that dupα7 probably reduces human vagal anti-inflammatory responses and suggest its involvement in other α7-nAChR-mediated pathophysiological processes.
Adler,
Quantifying colocalization by correlation: the Pearson correlation coefficient is superior to the Mander's overlap coefficient.
2010, Pubmed
Adler,
Quantifying colocalization by correlation: the Pearson correlation coefficient is superior to the Mander's overlap coefficient.
2010,
Pubmed
Albuquerque,
Mammalian nicotinic acetylcholine receptors: from structure to function.
2009,
Pubmed
Araud,
The chimeric gene CHRFAM7A, a partial duplication of the CHRNA7 gene, is a dominant negative regulator of α7*nAChR function.
2011,
Pubmed
,
Xenbase
Arias,
Role of non-neuronal nicotinic acetylcholine receptors in angiogenesis.
2009,
Pubmed
Baird,
Up-regulation of the human-specific CHRFAM7A gene in inflammatory bowel disease.
2016,
Pubmed
Benfante,
Expression of the α7 nAChR subunit duplicate form (CHRFAM7A) is down-regulated in the monocytic cell line THP-1 on treatment with LPS.
2011,
Pubmed
Bolte,
A guided tour into subcellular colocalization analysis in light microscopy.
2006,
Pubmed
Bordas,
Expression patterns for nicotinic acetylcholine receptor subunit genes in smoking-related lung cancers.
2017,
Pubmed
Borovikova,
Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin.
2000,
Pubmed
Casey,
A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder.
2012,
Pubmed
Cedillo,
Usefulness of α7 nicotinic receptor messenger RNA levels in peripheral blood mononuclear cells as a marker for cholinergic antiinflammatory pathway activity in septic patients: results of a pilot study.
2015,
Pubmed
Costantini,
CHRFAM7A, a human-specific and partially duplicated α7-nicotinic acetylcholine receptor gene with the potential to specify a human-specific inflammatory response to injury.
2015,
Pubmed
Dajas-Bailador,
Nicotinic acetylcholine receptors and the regulation of neuronal signalling.
2004,
Pubmed
de Jonge,
The alpha7 nicotinic acetylcholine receptor as a pharmacological target for inflammation.
2007,
Pubmed
De Luca,
Regulation of alpha7-nicotinic receptor subunit and alpha7-like gene expression in the prefrontal cortex of patients with bipolar disorder and schizophrenia.
2006,
Pubmed
de Lucas-Cerrillo,
Function of partially duplicated human α77 nicotinic receptor subunit CHRFAM7A gene: potential implications for the cholinergic anti-inflammatory response.
2011,
Pubmed
,
Xenbase
Dineley,
Nicotinic ACh receptors as therapeutic targets in CNS disorders.
2015,
Pubmed
Dunn,
A practical guide to evaluating colocalization in biological microscopy.
2011,
Pubmed
Fasoli,
Structure of neuronal nicotinic receptors.
2015,
Pubmed
Freedman,
Linkage disequilibrium for schizophrenia at the chromosome 15q13-14 locus of the alpha7-nicotinic acetylcholine receptor subunit gene (CHRNA7).
2001,
Pubmed
García-Guzmán,
Role of two acetylcholine receptor subunit domains in homomer formation and intersubunit recognition, as revealed by alpha 3 and alpha 7 subunit chimeras.
1994,
Pubmed
,
Xenbase
Gault,
Genomic organization and partial duplication of the human alpha7 neuronal nicotinic acetylcholine receptor gene (CHRNA7).
1998,
Pubmed
Gault,
Comparison of polymorphisms in the alpha7 nicotinic receptor gene and its partial duplication in schizophrenic and control subjects.
2003,
Pubmed
Hong,
Association study of the human partially duplicated alpha7 nicotinic acetylcholine receptor genetic variant with bipolar disorder.
2004,
Pubmed
Huston,
Transcutaneous vagus nerve stimulation reduces serum high mobility group box 1 levels and improves survival in murine sepsis.
2007,
Pubmed
Kim,
Stimulation of the α7 nicotinic acetylcholine receptor protects against sepsis by inhibiting Toll-like receptor via phosphoinositide 3-kinase activation.
2014,
Pubmed
Knaus,
APACHE II: a severity of disease classification system.
1985,
Pubmed
Kracun,
Influence of the M3-M4 intracellular domain upon nicotinic acetylcholine receptor assembly, targeting and function.
2008,
Pubmed
Li,
The adaptor Grb7 is a novel calmodulin-binding protein: functional implications of the interaction of calmodulin with Grb7.
2005,
Pubmed
Locke,
Refinement of a chimpanzee pericentric inversion breakpoint to a segmental duplication cluster.
2003,
Pubmed
Maldifassi,
A new IRAK-M-mediated mechanism implicated in the anti-inflammatory effect of nicotine via α7 nicotinic receptors in human macrophages.
2014,
Pubmed
Mukherjee,
Mutations of cytosolic loop residues impair assembly and maturation of alpha7 nicotinic acetylcholine receptors.
2009,
Pubmed
Pillai,
α7 nicotinic acetylcholine receptor subunit in angiogenesis and epithelial to mesenchymal transition.
2012,
Pubmed
Riley,
A 3-Mb map of a large Segmental duplication overlapping the alpha7-nicotinic acetylcholine receptor gene (CHRNA7) at human 15q13-q14.
2002,
Pubmed
Rosas-Ballina,
Splenic nerve is required for cholinergic antiinflammatory pathway control of TNF in endotoxemia.
2008,
Pubmed
Rosas-Ballina,
Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit.
2011,
Pubmed
Schuller,
Regulatory role of the α7nAChR in cancer.
2012,
Pubmed
Serantes,
Interleukin-1beta enhances GABAA receptor cell-surface expression by a phosphatidylinositol 3-kinase/Akt pathway: relevance to sepsis-associated encephalopathy.
2006,
Pubmed
,
Xenbase
Severance,
Differentiating nicotine- versus schizophrenia-associated decreases of the alpha7 nicotinic acetylcholine receptor transcript, CHRFAM7A, in peripheral blood lymphocytes.
2009,
Pubmed
Singh,
Nicotinic acetylcholine receptor signaling in tumor growth and metastasis.
2011,
Pubmed
Solís-Garrido,
Cross-talk between native plasmalemmal Na+/Ca2+ exchanger and inositol 1,4,5-trisphosphate-sensitive ca2+ internal store in Xenopus oocytes.
2004,
Pubmed
,
Xenbase
Tracey,
Physiology and immunology of the cholinergic antiinflammatory pathway.
2007,
Pubmed
Unwin,
Refined structure of the nicotinic acetylcholine receptor at 4A resolution.
2005,
Pubmed
Wang,
Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis.
2004,
Pubmed
Wang,
Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation.
2003,
Pubmed
Wang,
The duplicated α7 subunits assemble and form functional nicotinic receptors with the full-length α7.
2014,
Pubmed
Yang,
Acetylcholine Inhibits LPS-Induced MMP-9 Production and Cell Migration via the α7 nAChR-JAK2/STAT3 Pathway in RAW264.7 Cells.
2015,
Pubmed
Zhang,
Role of α7-nicotinic acetylcholine receptor in nicotine-induced invasion and epithelial-to-mesenchymal transition in human non-small cell lung cancer cells.
2016,
Pubmed
