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Fig. 1 | Acta Neuropathologica Communications

Fig. 1

From: The Alzheimer susceptibility gene BIN1 induces isoform-dependent neurotoxicity through early endosome defects

Fig. 1

Functional conservation of human BIN1 isoforms in Drosophila. a Scheme of cerebral human BIN1 isoform1 (BIN1iso1), muscular human BIN1 isoform8 (BIN1iso8), ubiquituous human BIN1 isoform9 (BIN1iso9) and Drosophila BIN1, called Amphiphysin, isoformA (dAmphA) for which transgenic lines were generated. b Western blot analysis of Amph and BIN1 expression in dAmphMI08903-TG4.0/+, dAmphMI08903-TG4.0/5E3 and dAmphMI08903-TG4.0/+; UAS-BIN1iso8 fly thorax. dAmphA, dAmphB and dAmphC were expressed in the heterozygous dAmphMI08903/+ flies, whereas they were not detected in dAmphMI08903/5E3 flies (*background staining). BIN1iso8 was expressed in dAmphMI08903-TG4.0/+; UAS-BIN1iso8 flies. c Analysis of the climbing locomotor activity of 2 day-old flies with the indicated genotype. dAmphMI08903-TG4.0/5E3 flies exhibited a similar low climbing score as the null dAmph5E3/5E3flies. Expression of BIN1iso8 rescued the locomotor defects of dAmphMI08903-TG4.0/5E3 flies (from left to right n = 10, 5, 49, 67, 26, ANOVA F-value = 66.15, Df = 4, p = 2.37 × 10−38 with post-hoc Tukey, n.s. not significant). d Visualization of outer photoreceptor neuron rhabdomeres by cornea neutralization in 2-day-old flies expressing mCherry (as a control), BIN1iso1, BIN1iso8, BIN1iso9 and dAmphA under a GMR driver (attP2 is a control with an empty attP2 landing site and no UAS construct). While each ommatidium contained 6 outer photorceptors organized in a trapezoid shape (yellow circles) in the two control conditions, BIN1 isoforms and dAmphA expression resulted in a strong alteration in the number, shape and trapezoid organization of the rhabdomeres with a stronger effect for BIN1iso1 and BIN1iso9 high-expressing lines. e Immunofluorescence of whole-mount pupal retina expressing Luciferase (as a control), BIN1iso1, BIN1iso8, BIN1iso9 or dAmphA. They were labelled for the plasma membrane neuronal Na/K ATPase and F-actin. Contrary to the control, BIN1iso1, BIN1iso8, BIN1iso9 and dAmphA induced a strong accumulation of F-actin at the level of the rhabdomere

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