Yes-associated protein upregulates filopodia formation to promote alveolar epithelial-cell phagocytosis.

Cells engulf particles larger than 0.5 μm in diameter by phagocytosis, which is driven by cytoskeletal rearrangements. Phagocytosis by alveolar epithelial cells (AECs) helps to maintain the alveolar homeostasis. Yes-associated protein (YAP), a transcriptional coactivator of the Hippo pathway, affects proliferation, differentiation, and cytoskeletal rearrangement of AECs, but it is not clear whether YAP regulates phagocytosis. In this study, interference with YAP expression inhibited phagocytosis in MLE-12 cells and in primary cultures of AEC. Filopodia formation promoted phagocytosis in AECs, and YAP enhanced filopodia formation in AECs. Blocking PI3K signaling resulted in reduced YAP protein expression and inhibition of phagocytosis. The results indicate that YAP expression was regulated by PI3K signaling and promoted phagocytosis in AECs by upregulating filopodia formation.