Department of Cell Biology, NYU Grossman School of Medicine, 550 First Avenue, New York, NY, 10016, USA.
Department of Cell Biology, NYU Grossman School of Medicine, 550 First Avenue, New York, NY, 10016, USA.
Dev Biol. 2021 Oct;478:205-211. doi: 10.1016/j.ydbio.2021.07.008. Epub 2021 Jul 13.
Ire1 is an endoplasmic reticulum (ER) transmembrane RNase that cleaves substrate mRNAs to help cells adapt to ER stress. Because there are cell types with physiological ER stress, loss of Ire1 results in metabolic and developmental defects in diverse organisms. In Drosophila, Ire1 mutants show developmental defects at early larval stages and in pupal eye photoreceptor differentiation. These Drosophila studies relied on a single Ire1 loss of function allele with a Piggybac insertion in the coding sequence. Here, we report that an Ire1 allele with a specific impairment in the RNase domain, H890A, unmasks previously unrecognized Ire1 phenotypes in Drosophila eye pigmentation. Specifically, we found that the adult eye pigmentation is altered, and the pigment granules are compromised in Ire1 homozygous mosaic eyes. Furthermore, the Ire1 mutant eyes had dramatically reduced Rhodopsin-1 protein levels. Drosophila eye pigment granules are most notably associated with late endosome/lysosomal defects. Our results indicate that the loss of Ire1, which would impair ER homeostasis, also results in altered adult eye pigmentation.
IRE1 是一种内质网 (ER) 跨膜 RNA 酶，可切割底物 mRNA，帮助细胞适应 ER 应激。由于存在具有生理 ER 应激的细胞类型，IRE1 的缺失会导致不同生物体的代谢和发育缺陷。在果蝇中，IRE1 突变体在早期幼虫阶段和蛹眼光感受器分化中表现出发育缺陷。这些果蝇研究依赖于编码序列中插入 Piggybac 的单个 IRE1 功能丧失等位基因。在这里，我们报告说，一种在 RNase 结构域中具有特定损伤的 IRE1 等位基因，H890A，揭示了果蝇眼睛色素沉着中以前未被识别的 IRE1 表型。具体来说，我们发现成年眼睛的色素沉着发生改变，并且在 IRE1 纯合镶嵌眼中的色素颗粒受损。此外，IRE1 突变体眼睛中的 Rhodopsin-1 蛋白水平显著降低。果蝇眼睛色素颗粒最显著地与晚期内体/溶酶体缺陷相关。我们的结果表明，内质网稳态受损的 IRE1 缺失也会导致成年眼睛色素沉着的改变。
