Lachowicz-Scroggins Marrah E, Gordon Erin D, Wesolowska-Andersen Agata, Jackson Nathan D, MacLeod Hannah J, Sharp Louis Z, Sun Matthew, Seibold Max A, Fahy John V
1Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143 USA.
2Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, San Francisco, CA 94143 USA.
Cell Discov. 2018 Feb 13;4:7. doi: 10.1038/s41421-017-0006-x. eCollection 2018.
Polarization of the airway epithelial cells (AECs) in the airway lumen is critical to the proper function of the mucociliary escalator and maintenance of lung health, but the cellular requirements for polarization of AECs are poorly understood. Using human AECs and cell lines, we demonstrate that cadherin-26 (CDH26) is abundantly expressed in differentiated AECs, localizes to the cell apices near ciliary membranes, and has functional cadherin domains with homotypic binding. We find a unique and non-redundant role for CDH26, previously uncharacterized in AECs, in regulation of cell-cell contact and cell integrity through maintaining cytoskeletal structures. Overexpression of CDH26 in cells with a fibroblastoid phenotype increases contact inhibition and promotes monolayer formation and cortical actin structures. CDH26 expression is also important for localization of planar cell polarity proteins. Knockdown of CDH26 in AECs results in loss of cortical actin and disruption of CRB3 and other proteins associated with apical polarity. Together, our findings uncover previously unrecognized functions for CDH26 in the maintenance of actin cytoskeleton and apicobasal polarity of AECs.
气道腔内气道上皮细胞（AECs）的极化对于黏液纤毛运输系统的正常功能以及肺部健康的维持至关重要，但AECs极化的细胞需求仍知之甚少。利用人AECs和细胞系，我们证明钙黏蛋白-26（CDH26）在分化的AECs中大量表达，定位于靠近纤毛膜的细胞顶端，并且具有具有同型结合的功能性钙黏蛋白结构域。我们发现CDH26在AECs中以前未被描述的在通过维持细胞骨架结构来调节细胞间接触和细胞完整性方面具有独特且非冗余的作用。在具有成纤维细胞样表型的细胞中过表达CDH26可增加接触抑制并促进单层形成和皮质肌动蛋白结构。CDH26的表达对于平面细胞极性蛋白的定位也很重要。在AECs中敲低CDH26会导致皮质肌动蛋白丧失以及CRB3和其他与顶端极性相关的蛋白质的破坏。总之，我们的研究结果揭示了CDH26在维持AECs肌动蛋白细胞骨架和顶基极性方面以前未被认识的功能。
