Removing the EGF repeats
from the ff-synNotch ligands and receptors
does not compensate for the lack of the ligand ICD. (A,D) Schematics
of the ff-synNotch systems containing either ligands lacking the EGF
(1–8) repeats in their ECD (A), or receptors lacking the EGF
(24–36) repeats in their ECD (D). (B,E) Luciferase activity
assay showing the activation of Notch reporter cell lines (U2OS cells
stably expressing the receptors indicated in A,D and transfected with
a luciferase reporter) co-cultured with CHO-TetR cells expressing
different ligand variants corresponding to the constructs shown in
(A,D). (C,F) Images from a TEC assay where U2OS cells expressing Notch-citrine
variants were co-cultured with CHO-TetR cells expressing ligand variants
corresponding to the constructs shown in (A,D). Images were taken
10 h induction of ligand expression with 100 ng/mL dox followed by
1 h induction of binding with 250 nM rapamycin. TEC was observed with
full-length ligands (white arrows). Accumulation at the boundaries
of cell contact without TEC was observed with ligands lacking their
ICD (orange arrows). Data points show mean values from n = 14 measurements
for (B,E) from four independent experiments. Error bars represent
S.E.M. ***p < 0.001. Scale bars-10 μm.