GMR regulatory sequences drive expression of a γ-secretase reporter. The reporter consists of a cleavable signal sequence, followed by a C-terminal fragment of Hsap\APP that starts immediately downstream of the β-cleavage site (residue 671) and that also lacks a stop codon. The GAL4 coding region is fused to the C-terminus of the Hsap\APP sequences. In the absence of γ-secretase, the GAL4 coding sequence is tethered at the membrane by the Hsap\APP sequences. In the presence of γ-secretase, cleavage of the Hsap\APP protein sequence releases from the membrane a fragment consisting of the intracellular domain of Hsap\APP and the GAL4 coding region, allowing expression of UAS-containing constructs driven by the GAL4 driver.
ScerGAL4GMR.APP drives expression in presumptive photoreceptor cells in the eye disc; the ScerGAL4 protein is tethered to the cell membrane by HsapAPP, and cannot enter the nucleus to drive expression until cleaved by gamma-secretase.
