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Delta/Notch-Like EGF-Related Receptor (DNER) Is Not a Notch Ligand

PLoS ONE (2016) 11(9)
DOI: 10.1371/journal.pone.0161157
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Abstract

Delta/Notch-like EGF-related receptor (DNER) has been reported to act as a Notch ligand, despite lacking a Delta/Serrate/Lag (DSL) binding domain common to all other known ligands. The established Notch ligand Delta-like 1 (DLL1), but not DNER, activated Notch1 in a luciferase assay, prevented the differentiation of myoblasts through Notch signaling, and bound Notch-fc in a cell-based assay. DNER is not a Notch ligand and its true function remains unknown.

Figures

  • Fig 1. DNERdoes not activate, functionwith, or bind toNotch, but knownNotch ligandDLL1does. (A) Pooled luciferase results from4 separate experiments (normalized to themean of empty vector in each experiment). U2OS cells were transfected with ligand (DLL1,DNER, or EV), and separately a population of U2OS cells was transfected to express Notch, the control luciferaseRenilla, and TP1, a promoter that expresses firefly luciferase whenNotch is activated. The two populationswere cocultured24 hours after transfection (trans configuration), and activity read after an additional 24–48 hours of incubation. (B) C2C12 cells (myoblasts) were incubatedwith differentiationmedia (2% horse serum) that either had pre-clusteredDLL1-fc (1:1), pre-clusteredDNER-fc (1:1), un-clusteredDNER-fc, or fc only, all at a ratio of 1:150 in media. Cells were incubated for 72 hours, then fixed, and stained for the presence of myosin heavy chain (MHC) and nuclei. By measuring the percent of total nuclei that were inside of differentiatedMHCpositive myotubes, fusion indexes were calculated. (C) DNER (top left, green) transfected U2OS cells were not labeled by pre-clustered Notch-fc (topmiddle, red) but DLL1 (bottom left, green) transfected U2OS cells were labeled by pre-clusteredNotch-fc (bottommiddle, red).Merged images are shown at far right. Scale 10 μM. **** = p value <0.0001.*** = p value 0.002. ns = not significant. DLL1 = Delta-like 1, a known Notch Ligand,DNER =Delta/Notch-like epidermal growth factor (EGF) related receptor, GSI = γ-secretase inhibitor, fc only = rabbit anti-human-fc.

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CITATION STYLE

APA

Greene, M., Lai, Y., Pajcini, K., Bailis, W., Pear, W. S., & Lancaster, E. (2016). Delta/Notch-Like EGF-Related Receptor (DNER) Is Not a Notch Ligand. PLoS ONE, 11(9). https://doi.org/10.1371/journal.pone.0161157

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