Planar Cell Polarity protein network, which controls ciliogenesis and cilia function, is altered in Human Cystic Fibrosis Bronchial Epithelial cells.
(2013) 10th ECFS Basic Science — Location: Malaga, Spain (20.March.2013)
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- Mucociliary clearance (MCC), abnormal in CF, is physiologically regulated by epithelial ion transport together with epithelial cilia movement and mechanical phenomenon such as cough and sneezing. Recently, new insights on ciliogenesis and cilia function have emerged. Planar Cell Polarity (PCP) is a tightly controlled protein network which drives the orientation of specialized structures (such as fly wings, mammal furs or fish scales) within the plane of the epithelial tissue. PCP has been described in mammal lung epithelial cells as a crucial mechanism controlling ciliogenesis and cilia function. Cilia structure and function have been studies in CF. Although the majority of these studies showed no structural abnormality and a normal cilia beat frequency (CBF), it has also been showed that ciliary disorientation, rather than ultrastructural abnormalities or slow CBF, may occur secondary to lung inflammation and result in delayed MCC. We hypothesized that CF HBEs may display abnormalities in PCP network which could further impair coordinated cilia function in the plan of the epithelium. We demonstrated that HBEs expressed several PCP genes. Among them, expression of CELSR3 (Cadherin EGF LAG seven-pass G-type receptor 3) and Vangl-1 (Van-Gogh like 1) was down-regulated in CF (F508del/F508del) HBEs as compared to non-CF cells. In contrast, Fz3 (Frizzled 3), Fz6, Pk1 (Prickle 1) and Vangl-2 were upregulated in CF cells. Very low levels of CELSR3 protein were found in CF cells; moreover we observed that CELSR3 does not undergo autoproteolytic cleavage (in the endoplasmic reticulum) nor N-glycosylation (in the Golgi apparatus) as it normally does in normal HBEs. These results suggest that expression and processing of PCP proteins is abnormal in CF-HBEs and may altered coordinated function of cilia within the bronchial epithelium in Cystic Fibrosis.
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Delbart, W., Dhooghe, B., Wallemacq, P., Lebecque, P., Leal, T., & Noël, S. (2013). Planar Cell Polarity protein network, which controls ciliogenesis and cilia function, is altered in Human Cystic Fibrosis Bronchial Epithelial cells. 10th ECFS Basic Science, Malaga, Spain. https://hdl.handle.net/2078.5/205588