Abstract
Expansions of polygutamine-encoding stretches in several genes cause neurodegenerative disorders including Huntington's Disease and Spinocerebellar Ataxia type 3. Expression of the human disease alleles in Drosophila melanogaster neurons recapitulates cellular features of these disorders, and has therefore been used to model the cell biology of these diseases. Here, we show that polyglutamine disease alleles expressed in Drosophila photoreceptors disrupt actin structure at rhabdomeres, as other groups have shown they do in Drosophila and mammalian dendrites. We show this actin regulatory pathway works through the small G protein Rac and the actin nucleating protein Form3. We also find that Form3 has additional functions in photoreceptors, and that loss of Form3 results in the specification of extra photoreceptors in the eye.
Highlights
Polyglutamine disorders are dominant neurodegenerative diseases caused by expanded CAG nucleotide tracts within protein coding genes (Orr and Zoghbi, 2007)
We show that polyglutamine disease alleles expressed in Drosophila photoreceptors disrupt actin structure at rhabdomeres, as other groups have shown they do in Drosophila and mammalian dendrites
Phalloidin staining reveals the structure of the rhabdomeres, as well as cortical actin underlying the rest of the plasma membrane (Fig. 1A, purple).We expressed full-length human polyQ proteins in photoreceptor cells using GMR-Gal4, and analyzed actin structure by staining eyes with phalloidin
Summary
Polyglutamine (polyQ) disorders are dominant neurodegenerative diseases caused by expanded CAG nucleotide tracts within protein coding genes (Orr and Zoghbi, 2007). The fruit fly Drosophila melanogaster has been a powerful model system for investigating the cellular and molecular mechanisms of these diseases (McGurk et al, 2015). Researchers have expressed expanded, pathogenic alleles of polyQ genes in Drosophila neurons to study their cellular responses, while expressing short, wild type alleles as a control. Expressing human disease alleles in fly neurons causes defects that are similar to those seen in the corresponding disease (Jackson et al, 1998; McGurk et al, 2015; Warrick et al, 1998)
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