National Creative Research Initiatives Center for Energy Homeostasis Regulation, Institute of Molecular Biology and Genetics, Seoul National University, 1 Gwanak-Ro, Gwanak-Gu, Seoul, 08826, Republic of Korea.
Harvard Medical School, Department of Cell Biology, 240 Longwood Avenue, Seeley-Mudd Building, Boston, MA, 02115, USA.
Sci Rep. 2017 Dec 18;7(1):17700. doi: 10.1038/s41598-017-17961-3.
Genetic mechanisms for the pathogenesis of visceral myopathy (VM) have been rarely demonstrated. Here we report the visceral role of misato (mst) in Drosophila and its implications for the pathogenesis of VM. Depletion of mst using three independent RNAi lines expressed by a pan-muscular driver elicited characteristic symptoms of VM, such as abnormal dilation of intestinal tracts, reduced gut motility, feeding defects, and decreased life span. By contrast, exaggerated expression of mst reduced intestine diameters, but increased intestinal motilities along with thickened muscle fibers, demonstrating a critical role of mst in the visceral muscle. Mst expression was detected in the adult intestine with its prominent localization to actin filaments and was required for maintenance of intestinal tubulin and actomyosin structures. Consistent with the subcellular localization of Mst, the intestinal defects induced by mst depletion were dramatically rescued by exogenous expression of an actin member. Upon ageing the intestinal defects were deteriorative with marked increase of apoptotic responses in the visceral muscle. Taken together, we propose the impairment of actomyosin structures induced by mst depletion in the visceral muscle as a pathogenic mechanism for VM.
内脏肌病（VM）的发病机制中的遗传机制很少被证明。在这里，我们报告了 mst 在果蝇中的内脏作用及其对 VM 发病机制的影响。使用通过泛肌肉驱动表达的三个独立的 RNAi 线耗尽 mst 会引起 VM 的特征性症状，例如肠道异常扩张、肠道蠕动减少、进食缺陷和寿命缩短。相比之下，mst 的过度表达会减小肠道直径，但会增加肠道蠕动，同时使肌肉纤维变厚，表明 mst 在内脏肌肉中起着关键作用。mst 在成年肠道中表达，其明显定位于肌动蛋白丝，并需要维持肠道微管蛋白和肌动球蛋白结构。与 Mst 的亚细胞定位一致，通过外源性表达肌动蛋白成员，mst 耗尽引起的肠道缺陷得到了显著挽救。随着年龄的增长，肠道缺陷恶化，内脏肌肉中的凋亡反应明显增加。总之，我们提出了 mst 耗尽引起的内脏肌动球蛋白结构损伤作为 VM 的发病机制。
