Department of Physiology, Dean A. McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Department of Ophthalmology, Dean A. McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Adv Exp Med Biol. 2023;1415:249-256. doi: 10.1007/978-3-031-27681-1_36.
Caveolin-1 (Cav1), the core structural and scaffolding protein of caveolae membrane domains, is highly expressed in many retinal cells and is associated with ocular diseases. Cav1 regulates innate immune responses and is implicated in neuroinflammatory and neuroprotective signaling in the retina. We have shown that Cav1 expression in Müller glia accounts for over 70% of all retinal Cav1 expression. However, the proteins interacting with Cav1 in Müller glia are not established. Here, we show that immortalized MIO-M1 Müller glia, like endogenous Müller glia, highly express Cav1. Surprisingly, we found that Cav1 in MIO-M1 cells exists as heat-resistant, high molecular weight complexes that are stable after immunoprecipitation (IP). Mass spectrometric analysis of high molecular weight Cav1 complexes after Cav1 IP revealed an interactome network of intermediate filament, desmosomes, and actin-, and microtubule-based cytoskeleton. These results suggest Cav1 domains in Müller glia act as a scaffolding nexus for the cytoskeleton.
窖蛋白-1(Cav1)是质膜窖结构和支架蛋白,在许多视网膜细胞中高度表达,与眼部疾病有关。Cav1 调节先天免疫反应,并参与视网膜中的神经炎症和神经保护信号。我们已经表明,Müller 胶质细胞中的 Cav1 表达占视网膜中所有 Cav1 表达的 70%以上。然而,与 Müller 胶质细胞中的 Cav1 相互作用的蛋白质尚未确定。在这里,我们表明,与内源性 Müller 胶质细胞一样,永生化的 MIO-M1 Müller 胶质细胞高度表达 Cav1。令人惊讶的是,我们发现 MIO-M1 细胞中的 Cav1 存在为耐热的高分子量复合物,在免疫沉淀(IP)后稳定。Cav1 IP 后高分子量 Cav1 复合物的质谱分析揭示了中间丝、桥粒以及基于肌动蛋白和微管的细胞骨架的相互作用网络。这些结果表明,Müller 胶质细胞中的 Cav1 结构域充当细胞骨架的支架连接点。