State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, The Innovative Academy of Seed Design, Chinese Academy of Sciences, Beijing, 100101, China.
Institute of Forensic Medicine and Laboratory Medicine, Jining Medical University, Jining, 272067, China.
Sci China Life Sci. 2022 Jan;65(1):193-205. doi: 10.1007/s11427-020-1875-x. Epub 2021 Mar 16.
Pulmonary surfactant is a lipid-protein complex secreted by alveolar type II epithelial cells and is essential for the maintenance of the delicate structure of mammalian alveoli to promote efficient gas exchange across the air-liquid barrier. The Golgi apparatus plays an important role in pulmonary surfactant modification and secretory trafficking. However, the physiological function of the Golgi apparatus in the transport of pulmonary surfactants is unclear. In the present study, deletion of GM130, which encodes for a matrix protein of the cis-Golgi cisternae, was shown to induce the disruption of the Golgi structure leading to impaired secretion of lung surfactant proteins and lipids. Specifically, the results of in vitro and in vivo analysis indicated that the loss of GM130 resulted in trapping of Sftpa in the endoplasmic reticulum, Sftpb and Sftpc accumulation in the Golgi apparatus, and an increase in the compensatory secretion of Sftpd. Moreover, global and epithelial-specific GM130 knockout in mice resulted in an enlargement of alveolar airspace and an increase in alveolar epithelial autophagy; however, surfactant repletion partially rescued the enlarged airspace defects in GM130-deficient mice. Therefore, our results demonstrate that GM130 and the mammalian Golgi apparatus play a critical role in the control of surfactant protein secretion in pulmonary epithelial cells.
肺表面活性剂是由肺泡 II 型上皮细胞分泌的一种脂-蛋白复合物，对于维持哺乳动物肺泡的精细结构、促进气-液界面的高效气体交换至关重要。高尔基器在肺表面活性剂的修饰和分泌运输中起着重要作用。然而，高尔基器在肺表面活性剂运输中的生理功能尚不清楚。本研究表明，编码顺式高尔基池基质蛋白的 GM130 缺失会诱导高尔基结构的破坏，导致肺表面活性剂蛋白和脂质分泌受损。具体而言，体外和体内分析的结果表明，GM130 的缺失导致 Sftpa 在内质网中被截留，Sftpb 和 Sftpc 在高尔基器中积累，以及 Sftpd 的代偿性分泌增加。此外，在小鼠中进行的全局和上皮特异性 GM130 敲除导致肺泡气腔增大和肺泡上皮细胞自噬增加；然而，表面活性剂补充部分挽救了 GM130 缺陷小鼠中增大的气腔缺陷。因此，我们的结果表明，GM130 和哺乳动物高尔基器在控制肺上皮细胞表面活性剂蛋白分泌中起着关键作用。
