Minimal ff-synNotch systems require the ligand ICD. (A,D)
Schematics
of the minimal ff-synNotch systems where both ligand TM domain (A)
and EGF (1–8) repeats (D) are changed as indicated. Receptors
lack the EGF (24–36) repeats. (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 after 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 on the boundaries, but no TEC
were observed in 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 < 0.05, **p < 0.01, ***p < 0.001. Scale bars-10 μm.