University of San Diego, Department of Biology, 5998 Alcala Park Blvd, SCST 372, San Diego, CA 92110, USA.
University of San Diego, Department of Biology, 5998 Alcala Park Blvd, SCST 372, San Diego, CA 92110, USA.
Mol Cell Neurosci. 2018 Dec;93:10-17. doi: 10.1016/j.mcn.2018.08.005. Epub 2018 Aug 24.
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.
在几个基因中，聚谷氨酰胺编码序列的扩展导致神经退行性疾病，包括亨廷顿病和脊髓小脑共济失调 3 型。在果蝇神经元中表达人类疾病等位基因重现了这些疾病的细胞特征，因此被用于模拟这些疾病的细胞生物学。在这里，我们表明，在果蝇光感受器中表达的聚谷氨酰胺疾病等位基因破坏了嵴状结构中的肌动蛋白结构，正如其他研究小组在果蝇和哺乳动物树突中所表明的那样。我们表明，这条肌动蛋白调节途径通过小 G 蛋白 Rac 和肌动蛋白成核蛋白 Form3 发挥作用。我们还发现 Form3 在光感受器中具有其他功能，并且 Form3 的缺失导致眼睛中额外的光感受器的特化。
