Figure 3
From: Increased expression of BIN1 mediates Alzheimer genetic risk by modulating tau pathology
Amph modifies Tau neurotoxicity in Drosophila. (a) Schematic showing evolutionary conservation of the protein domains of Drosophila Amph and human BIN1 isoforms (iso.). BAR, BIN1-amphiphysin-Rvs167; CLAP, clathrin and AP-2 binding; MBD, Myc-binding domain; SH3, Src homology 3. PI, phosphoinositide binding region. (b) External eye morphology. (i) GMR/+ control (outcrossed eye specific GMR-GAL driver) showing normal regular eye morphology; (ii) GMR>Tau (Tau control, eye specific overexpression of Tau) showing severely reduced eye size and external roughness; (iii) GMR>Tau>AmphKD (simultaneous eye-specific overexpression of Tau and knockdown of Amph) showing increased eye size compared with (ii). (c) Quantification of eye size in flies overexpressing Tau alone (GMR>Tau) and simultaneous decreased Amph expression by either RNAi-mediated knockdown (GMR>Tau>AmphKD) or by removal of one genomic copy of Amph (GMR>Tau;Amph5E3/+). (d) Notal bristle number. (i) Eq/+ (control, outcrossed notal bristle specific Eq-GAL driver) showing normal number of bristles; (ii) Eq>Tau (Tau control, notal bristle specific overexpression of Tau) showing severely reduced number of bristles; (iii) Eq>Tau>AmphKD (simultaneous bristle specific overexpression of Tau and knockdown of Amph) increased number of bristles compared to (ii). (e) Quantification of notal bristle number in flies overexpressing Tau alone (Eq>Tau) and simultaneous decreased Amph expression by either RNAi-mediated knockdown (Eq>Tau>AmphKD) or removal of one genomic copy of Amph (Eq>Tau;Amph5E3/+). (f) Mushroom body morphology. (i) Immunohistochemical α−FasII labeling in whole-mount brains showing normal mushroom body morphology in a control brain (Elav/+, outcrossed neuron-specific Elav-GAL4 driver). α-, β- and γ-lobes and peduncles (arrowheads) are indicated; (ii) Neuron-specific Tau overexpression (Elav>Tau) ablates mushroom body lobes while peduncles can still be observed in most cases (arrowheads); (iii) Neuron-specific Tau overexpression and simultaneous Amph knockdown (Elav>Tau>AmphKD) reveals thin β-lobes in 13/19 brains (arrows); (iii) Elav>Tau>AmphKD shows morphologically normal mushroom bodies in 2/19 brains. (g) Quantification of the presence of mushroom body (MB) lobes in flies panneuronally overexpressing Tau alone (Elav>Tau) and simultaneous decreased Amph expression by RNAi-mediated knockdown (Elav>Tau>AmphKD). Histograms in c and e indicate means±s.e.m. *P<0.05; ***P<0.001.
