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Appears in Networks 1

In-Edges 9

a(CHEBI:nifedipine) causesNoChange act(p(HGNC:CHRNA7, var("p.345A"), var("p.346A"), var("p.347A"), var("p.348A"))) View Subject | View Object

In α7345–348A nAChR expressing cells, nifedipine had no effect on the peak or the duration of the calcium transient (peak: 957.00% ΔF/Fθ ± 252.2%; AUC: 333.33% ΔF/Fθ2 × s ± 91.53%) relative to choline treatment alone (Fig. 5, A–C). The findings suggest that choline-induced calcium responses in PC12 cells involve the activity of VGCC (37, 38). PubMed:26088141

a(MESH:"GP Antagonist-2A peptide") causesNoChange act(p(HGNC:CHRNA7, var("p.345A"), var("p.346A"), var("p.347A"), var("p.348A"))) View Subject | View Object

SP pretreatment did not significantly alter calcium peaks in α7345–348A nAChR expressing cells, showing a small (−31.24%) reduction in calcium responses relative to the α7345–348A baseline measure (p > 0.05). PubMed:26088141

a(MESH:"xestospongin C") decreases act(p(HGNC:CHRNA7, var("p.345A"), var("p.346A"), var("p.347A"), var("p.348A"))) View Subject | View Object

Xestospongin C treatment did not impact the calcium peak (628.87% ΔF/Fθ ± 69.43%) or total calcium transient (AUC: 443.86% ΔF/Fθ2 × s ± 54.72%; + xestospongin C = 340.39% ΔF/Fθ2 × s ± 96.99%) in α7345–348A expressing cells (α7 to α7 + xestospongin C, p = 0.017; α7 to α7345–348A, p = 0.013; α7 to α7345-348A + xestospongin C, p = 0.017) (Fig. 7, B and C). The data underscores the inability of α7345–348A nAChRs to activate intracellular calcium via IP3Rs (18). PubMed:26088141

a(MESH:Barium) causesNoChange act(p(HGNC:CHRNA7, var("p.345A"), var("p.346A"), var("p.347A"), var("p.348A"))) View Subject | View Object

As shown in Fig. 5, A–C, barium replacement had little to no effect on the peak and total calcium transient observed in α7 (peak: 1474.83% ΔF/Fθ ± 162.00%; AUC: 693.5% ΔF/Fθ2 × s ± 154.15%) and α7345–348A expressing cells (peak: 794% ΔF/Fθ ± 81.36%; AUC: 543.5% ΔF/Fθ2 × s ± 89.59%). PubMed:26088141

g(HGNC:CHRNA7, var("p.345A"), var("p.346A"), var("p.347A"), var("p.348A")) causesNoChange p(HGNC:CHRNA7, var("p.345A"), var("p.346A"), var("p.347A"), var("p.348A")) View Subject | View Object

Studies in N2a cells indicate that transfection with α7345–348A yields a similar α7 nAChR expression as the wild-type (α7) and supports the finding that mutation at the GPBC does not impact the synthesis of the nAChR in cells. PubMed:26088141

Out-Edges 14

p(HGNC:CHRNA7, var("p.345A"), var("p.346A"), var("p.347A"), var("p.348A")) decreases bp(GO:"calcium-mediated signaling") View Subject | View Object

These findings in N2a cells are consistent with data from PC12 cells and suggest that α7345–348A nAChR expression impairs nAChR calcium signaling. PubMed:26088141

p(HGNC:CHRNA7, var("p.345A"), var("p.346A"), var("p.347A"), var("p.348A")) increases p(HGNC:CHRNA7) View Subject | View Object

Western blot analysis confirms that transfection of α7 nAChRs augments total α7 subunit expression in PC12 cells, which express endogenous α7 nAChRs. Transfection with α7 (α7+) increased the immunoreactive α7 signal by over 60% from endogenous mock-transfected control cells, whereas transfection with the mutant α7345–348A increased the total α7 signal by 48% over the endogenous α7 from control cells (Fig. 3A). PubMed:26088141

p(HGNC:CHRNA7, var("p.345A"), var("p.346A"), var("p.347A"), var("p.348A")) directlyDecreases complex(p(HGNC:CHRNA7, var("p.345A"), var("p.346A"), var("p.347A"), var("p.348A")), p(HGNC:GNAQ)) View Subject | View Object

As shown in Fig. 3A, coupling between Gαq and α7 nAChRs was virtually abolished by expression of α7345–348A. A noticeable loss in Gαq (−62.18%) and Gβγ (−20.03%) expression within the α7 nAChR complex IP was seen in cells transfected with α7345–348A (Fig. 3A). PubMed:26088141

p(HGNC:CHRNA7, var("p.345A"), var("p.346A"), var("p.347A"), var("p.348A")) directlyDecreases complex(p(HGNC:CHRNA7, var("p.345A"), var("p.346A"), var("p.347A"), var("p.348A")), p(HGNC:GNAQ)) View Subject | View Object

An increase in G protein association within the α7 complex was observed in α7+ cells (Gαq +16.71%; Gβγ +19.90%) (Fig. 3A). Similar findings in transfected N2a cells indicate a loss in G protein association within the α7 complex when α7345–348A nAChRs are expressed (Fig. 3B). PubMed:26088141

p(HGNC:CHRNA7, var("p.345A"), var("p.346A"), var("p.347A"), var("p.348A")) directlyDecreases complex(p(HGNC:CHRNA7, var("p.345A"), var("p.346A"), var("p.347A"), var("p.348A")), p(HGNC:GNAQ)) View Subject | View Object

The data complements earlier findings on the ability of α7345–348A to function as a dominant negative blocker of G protein coupling in PC12 cells, and suggests that the GPBC directs nAChR association with Gαq and Gβγ. PubMed:26088141

p(HGNC:CHRNA7, var("p.345A"), var("p.346A"), var("p.347A"), var("p.348A")) directlyDecreases complex(p(FPLX:"G_beta"), p(FPLX:"G_gamma"), p(HGNC:CHRNA7, var("p.345A"), var("p.346A"), var("p.347A"), var("p.348A"))) View Subject | View Object

As shown in Fig. 3A, coupling between Gαq and α7 nAChRs was virtually abolished by expression of α7345–348A. A noticeable loss in Gαq (−62.18%) and Gβγ (−20.03%) expression within the α7 nAChR complex IP was seen in cells transfected with α7345–348A (Fig. 3A). PubMed:26088141

p(HGNC:CHRNA7, var("p.345A"), var("p.346A"), var("p.347A"), var("p.348A")) directlyDecreases complex(p(FPLX:"G_beta"), p(FPLX:"G_gamma"), p(HGNC:CHRNA7, var("p.345A"), var("p.346A"), var("p.347A"), var("p.348A"))) View Subject | View Object

An increase in G protein association within the α7 complex was observed in α7+ cells (Gαq +16.71%; Gβγ +19.90%) (Fig. 3A). Similar findings in transfected N2a cells indicate a loss in G protein association within the α7 complex when α7345–348A nAChRs are expressed (Fig. 3B). PubMed:26088141

p(HGNC:CHRNA7, var("p.345A"), var("p.346A"), var("p.347A"), var("p.348A")) directlyDecreases complex(p(FPLX:"G_beta"), p(FPLX:"G_gamma"), p(HGNC:CHRNA7, var("p.345A"), var("p.346A"), var("p.347A"), var("p.348A"))) View Subject | View Object

The data complements earlier findings on the ability of α7345–348A to function as a dominant negative blocker of G protein coupling in PC12 cells, and suggests that the GPBC directs nAChR association with Gαq and Gβγ. PubMed:26088141

p(HGNC:CHRNA7, var("p.345A"), var("p.346A"), var("p.347A"), var("p.348A")) decreases act(a(CHEBI:"calcium(2+)", loc(GO:intracellular))) View Subject | View Object

Xestospongin C treatment did not impact the calcium peak (628.87% ΔF/Fθ ± 69.43%) or total calcium transient (AUC: 443.86% ΔF/Fθ2 × s ± 54.72%; + xestospongin C = 340.39% ΔF/Fθ2 × s ± 96.99%) in α7345–348A expressing cells (α7 to α7 + xestospongin C, p = 0.017; α7 to α7345–348A, p = 0.013; α7 to α7345-348A + xestospongin C, p = 0.017) (Fig. 7, B and C). The data underscores the inability of α7345–348A nAChRs to activate intracellular calcium via IP3Rs (18). PubMed:26088141

p(HGNC:CHRNA7, var("p.345A"), var("p.346A"), var("p.347A"), var("p.348A")) decreases bp(MESH:"Pleckstrin Homology Domains") View Subject | View Object

In PC12 cells expressing α7345–348A nAChRs choline had a weak effect on PH-mCherry translocation relative to empty plasmid-transfected controls. Expression α7345–348A nAChRs was surprisingly associated with strong levels of PH-mCherry at the cell surface in the absence of drug treatment (Fig. 6B). PubMed:26088141

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BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.

If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.