Microtubules Enable the Planar Cell Polarity of Airway Cilia

Abstract

Summary Background Airway cilia must be physically oriented along the longitudinal tissue axis for concerted, directional motility that is essential for proper mucociliary clearance. Results We show that Planar Cell Polarity (PCP) signaling specifies directionality and orients respiratory cilia. Within all airway epithelial cells a conserved set of PCP proteins shows interdependent, asymmetric junctional localization; non-autonomous signaling coordinates polarization between cells; and a polarized microtubule (MT) network is likely required for asymmetric PCP protein localization. We find that basal bodies dock after polarity of PCP proteins is established, are polarized nearly simultaneously, and refinement of basal body/cilium orientation continues during airway epithelial development. Unique to mature multiciliated cells, we identify PCP-regulated, planar polarized MTs that originate from basal bodies and interact, via their plus ends, with membrane domains associated with the PCP proteins Frizzled and Dishevelled. Disruption of MTs leads to misoriented cilia. Conclusions A conserved PCP pathway orients airway cilia by communicating polarity information from asymmetric membrane domains at the apical junctions, through MTs, to orient the MT and actin based network of ciliary basal bodies below the apical surface.

Controlled levels of canonical Wnt signaling are required for neural crest migration

“…The atypical cadherin, Fmi resides on both distal and proximal edges, where it binds neighboring cells through heomophilic interactions (Usui et al, 1999;Shimada et al, 2001). Xenopus, zebrafish and the mouse, the same set of 'core PCP' proteins has been shown to regulate a plethora of early developmental events ranging from convergent extension movements during gastrulation, orientation of cochlear hair cell in the ear, neural tube closure, oriented cell division, lung branching, hair follicle alignment and polarized ciliary beating in the trachea and brain ventricles (Goodrich andStrutt, 2011, Gray et al, 2011;Zallen, 2007;Bosoi et al, 2011;De Marco et al, 2012;Kibar et al, 2009;Kibar et al, 2007;Rida and Chen, 2009;Wang and Nathans, 2007;Yates and Dean, 2007;Segalen and Bellaïche, 2009;Vladar et al, 2012) ( Fig.1.6.4.1). In all cases local modulation of cytoskeleton is crucial for the proper conduct of these processes.…”

Planar cell polarity in moving cells: think globally, act locally

“…With few exceptions, the relationship between core PCP components in vertebrate epithelial cells is the same as in flies, with Fzd and Dvl localizing together, opposite Vangl and Prickle (hereafter Pk) (Fig. 1B-D) (Butler and Wallingford, 2015;Chu and Sokol, 2016;Ciruna et al, 2006;Davey et al, 2016;Deans et al, 2007;Devenport et al, 2011;Hashimoto et al, 2010;Vladar et al, 2012;Yin et al, 2008). Altering the expression of Vang or Fz homologs mosaically in the frog skin or in the sensory epithelium of the chick ear disrupts the polarity of adjacent wild-type cells, suggesting that the molecular interactions between core PCP components that amplify and maintain their asymmetric localization are conserved between fly and vertebrate epithelia (Mitchell et al, 2009;Sienknecht et al, 2011).…”

“…PCP protein localization is also maintained intracellularly by localized protein degradation mediated by the E3 ubiquitin ligases Smurf1 and Smurf2, which are recruited to sites of activated Dvl2 where they target Pk1 for degradation (Narimatsu et al, 2009). A number of other proteins have been implicated in the (Vladar et al, 2012). In both multiciliated (dark gray spots) and surrounding cells, endogenous Vangl1, Pk2 and GFP-Pk1 (red) localize to the distal surface and GFP-Fzd3/6 and GFP-Dvl1/3 localize to the proximal surface.…”

Exploring the evolutionary history of centrosomes

“…Subdistal appendages are structurally similar to the basal foot that decorates centrioles in sponge choanocytes and in multiciliated cells from a variety of animal species, and indeed their assembly relies on at least one common component [101,105,106]. Like subdistal appendages, the basal foot anchors microtubules required for controlling the position of the centrioles within the plane of the membrane, which in turn determines ciliary beating orientation [105,107,108]. Unlike subdistal appendages, basal feet are observed in all basal metazoan lineages, suggesting that it is an ancestral trait associated with planar ciliary beating [109][110][111][112].…”