Kawaguchi Kotoku, Nakayama Shogo, Saito Daichi, Kogiso Haruka, Yasuoka Kasane, Marunaka Yoshinori, Nakahari Takashi, Asano Shinji
Department of Molecular Physiology, College of Pharmaceutical Sciences, Ritsumeikan University, Shiga 525-8577, Japan.
Laboratory for Lung Development and Regeneration, Riken Center for Biosystems Dynamics Research (BDR), Kobe 650-0047, Japan.
J Cell Sci. 2022 Mar 15;135(6). doi: 10.1242/jcs.259201. Epub 2022 Mar 16.
Mucociliary clearance, which is conducted by beating cilia cooperating with the surface mucous layer, is a major host defense mechanism of the airway epithelium. Ezrin, a crosslinker between membrane proteins and the actin cytoskeleton, is located in microvilli and around the basal bodies in airway ciliary cells. It is also likely that ezrin plays an important role in apical localization of β2 adrenergic receptor (β2AR) in airway ciliary cells. Here, we studied the physiological roles of ezrin by using trachea and airway epithelial cells prepared from ezrin-knockdown (Vil2kd/kd) mice. The trachea and airway ciliary cells of Vil2kd/kd mice presented a normal morphology and basal body orientation, suggesting that ezrin is not directly involved in development and planar cell polarity of cilia. Procaterol stimulates ciliary beating (frequency and amplitude) via β2AR in the airway ciliary cells. In the Vil2kd/kd mice, airway ciliary beating stimulated with procaterol was partly inhibited due to the impairment of cell surface expression of β2AR. These results suggest that ezrin regulates the beating of airway ciliary cells by promoting the apical surface localization of β2AR. This article has an associated First Person interview with the first author of the paper.
黏液纤毛清除是由纤毛摆动与表面黏液层协同完成的，是气道上皮的主要宿主防御机制。埃兹蛋白是一种膜蛋白与肌动蛋白细胞骨架之间的交联蛋白，位于气道纤毛细胞的微绒毛和基体周围。埃兹蛋白也可能在气道纤毛细胞中β2肾上腺素能受体（β2AR）的顶端定位中发挥重要作用。在此，我们通过使用从埃兹蛋白敲低（Vil2kd/kd）小鼠制备的气管和气道上皮细胞来研究埃兹蛋白的生理作用。Vil2kd/kd小鼠的气管和气道纤毛细胞呈现正常形态和基体方向，表明埃兹蛋白不直接参与纤毛的发育和平面细胞极性。丙卡特罗通过气道纤毛细胞中的β2AR刺激纤毛摆动（频率和幅度）。在Vil2kd/kd小鼠中，由于β2AR细胞表面表达受损，丙卡特罗刺激的气道纤毛摆动受到部分抑制。这些结果表明，埃兹蛋白通过促进β2AR的顶端表面定位来调节气道纤毛细胞的摆动。本文对该论文的第一作者进行了相关的第一人称访谈。
