The planar cell polarity (PCP) signaling pathway is a potent developmental regulator of directional cell behaviors such as migration, asymmetric division and morphological polarization that are critical for shaping the body axis and the complex three-dimensional architecture of tissues and organs. PCP is considered a noncanonical Wnt pathway due to the involvement of Wnt ligands and Frizzled family receptors in the absence of the beta-catenin driven gene expression observed in the canonical Wnt cascade. At the heart of the PCP mechanism are protein complexes capable of generating molecular asymmetries within cells along a tissue-wide axis that are translated into polarized actin and microtubule cytoskeletal dynamics. PCP has emerged as an important regulator of developmental, homeostatic and disease processes in the respiratory system. It acts along other signaling pathways to create the elaborately branched structure of the lung by controlling the directional protrusive movements of cells during branching morphogenesis. PCP operates in the airway epithelium to establish and maintain the orientation of respiratory cilia along the airway axis for anatomically directed mucociliary clearance. It also regulates the establishment of the pulmonary vasculature. In adult tissues, PCP dysfunction has been linked to a variety of chronic lung diseases such as cystic fibrosis, chronic obstructive pulmonary disease, and idiopathic pulmonary arterial hypertension, stemming chiefly from the breakdown of proper tissue structure and function and aberrant cell migration during regenerative wound healing. A better understanding of these (impaired) PCP mechanisms is needed to fully harness the therapeutic opportunities of targeting PCP in chronic lung diseases.
The cover image depicts a combination of a 3D reconstruction of ER-TGN contact sites by focus ion beam-scanning electron microscopy (FIB-SEM) and five images showing the visualization of the contacts by FRET/FLIM. The 3D reconstruction of the Golgi stack was generated from FIB-SEM tomography of a HepG2 cell using IMOD software. The ER cisterna is shown in red (with ribosomes as white circles), while the trans-most cisterna of the Golgi stack is shown in green (with emerging clathrin-coated buds decorated by pink dots). The five FLIM images are from HeLa cells expressing a TGN reporter (TGN46-GFP) and an ER reporter (mCherry-Cb5). The pseudocolour scale represents donor (i.e. GFP) lifetime (τ) values ranging from 1.8 (blue) to 2.7 ns (red) under conditions that destabilize (left) or stabilize ER-TGN contact sites. For further information, see the review by Venditti and colleagues (pp. 187–197). Image courtesy of Maria Antonietta De Matteis.
Noncanonical Wnt planar cell polarity signaling in lung development and disease
Eszter K. Vladar, Melanie Königshoff; Noncanonical Wnt planar cell polarity signaling in lung development and disease. Biochem Soc Trans 28 February 2020; 48 (1): 231–243. doi: https://doi.org/10.1042/BST20190597
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