Figure 9.

dBACE knockdown in neurons suppresses APPL-induced phenotypes. A, A Western blot using an anti-APPL serum against the intracellular domain reveals increased levels of the endogenous full-length APPL protein in dBACE knockdown flies compared with controls. B, Using the same C-terminal antibody reveals the two alternative C-terminal cleavage products of APPL in flies expressing APPL via GMR-GAL4: the α-cleaved CTF of 14.5 kDa and the 14 kDa β-CTF (lane 1). Inducing the dBACE^RNAi construct in GMR-GAL4; UAS-APPL flies reduces the levels of the β-CTF (lane 2), as does heterozygosity for dBACE⁵²⁴³ (lane 3). As expected, flies lacking APPL (Appl^d) show neither cleavage product (lane 4). A loading control using anti-β-tubulin is shown below each blot. C, Fast phototaxis assays reveal a dramatic decline in the PI of flies expressing APPL pan-neuronally using elav-GAL4, whereas their performance is substantially improved by expressing APPL in flies heterozygous for the dBACE⁵²⁴³ allele. D, Heterozygosity for dBACE⁵²⁴³also significantly enhances the viability of these flies. SEMs are indicated.