Department of Biology, University of Colorado Colorado Springs, Colorado Springs, CO, 80918, USA.
Department of Biomedical Sciences, Colorado State University, Fort Collins, CO, 80523, USA.
Dev Biol. 2021 May;473:15-32. doi: 10.1016/j.ydbio.2021.01.011. Epub 2021 Jan 27.
RNA-binding proteins play an important role in the regulation of post-transcriptional gene expression throughout the nervous system. This is underscored by the prevalence of mutations in genes encoding RNA splicing factors and other RNA-binding proteins in a number of neurodegenerative and neurodevelopmental disorders. The highly conserved alternative splicing factor Caper is widely expressed throughout the developing embryo and functions in the development of various sensory neural subtypes in the Drosophila peripheral nervous system. Here we find that caper dysfunction leads to aberrant neuromuscular junction morphogenesis, as well as aberrant locomotor behavior during larval and adult stages. Despite its widespread expression, our results indicate that caper function is required to a greater extent within the nervous system, as opposed to muscle, for neuromuscular junction development and for the regulation of adult locomotor behavior. Moreover, we find that Caper interacts with the RNA-binding protein Fmrp to regulate adult locomotor behavior. Finally, we show that caper dysfunction leads to various phenotypes that have both a sex and age bias, both of which are commonly seen in neurodegenerative disorders in humans.
RNA 结合蛋白在神经系统中发挥着重要作用，调节着转录后基因表达。这一点在许多神经退行性和神经发育障碍中得到了强调，这些疾病中存在编码 RNA 剪接因子和其他 RNA 结合蛋白的基因突变。高度保守的替代剪接因子 Caper 在整个发育胚胎中广泛表达，并在果蝇周围神经系统中各种感觉神经亚型的发育中发挥作用。在这里，我们发现 caper 功能障碍导致异常的神经肌肉接头形态发生，以及幼虫和成年阶段异常的运动行为。尽管它广泛表达，但我们的结果表明，caper 功能在神经系统中比在肌肉中更为重要，对于神经肌肉接头的发育和成年运动行为的调节都是必需的。此外，我们发现 Caper 与 RNA 结合蛋白 Fmrp 相互作用，以调节成年运动行为。最后，我们发现 caper 功能障碍导致了各种具有性别和年龄偏向的表型，这些表型在人类的神经退行性疾病中都很常见。
