Myosin Id is required for planar cell polarity in ciliated tracheal and ependymal epithelial cells

Abstract

In wild type (WT) tracheal epithelial cells, ciliary basal bodies are oriented such that all cilia on the cell surface beat in the same upward direction. This precise alignment of basal bodies and, as a result, the ciliary axoneme, is termed rotational planar cell polarity (PCP). Rotational PCP in the multi-ciliated epithelial cells of the trachea is perturbed in rats lacking myosin Id (Myo1d). Myo1d is localized in the F-actin and basal body rich subapical cortex of the ciliated tracheal epithelial cell. Scanning and transmission electron microscopy of Myo1d knock out (KO) trachea revealed that the unidirectional bending pattern is disrupted. Instead, cilia splay out in a disordered, often radial pattern. Measurement of the alignment axis of the central pair axonemal microtubules was much more variable in the KO, another indicator that rotational PCP is perturbed. The asymmetric localization of the PCP core protein Vangl1 is lost. Both the velocity and linearity of cilia-driven movement of beads above the tracheal mucosal surface was impaired in the Myo1d KO. Multi-ciliated brain ependymal epithelial cells exhibit a second form of PCP termed translational PCP in which basal bodies and attached cilia are clustered at the anterior side of the cell. The precise asymmetric clustering of cilia is disrupted in the ependymal cells of the Myo1d KO rat. While basal body clustering is maintained, left-right positioning of the clusters is lost.

Planar cell polarity in development and disease

“…Core PCP localization examined in these tissues reflects that seen in the fly wing; PK and VANGL occupy a domain complementary to that of DVL and FZ (Fig. 4A, C); however several additional cilia-associated proteins not found in D. melanogaster are required for normal core PCP protein localization in MCCs, including the myosin motor Myo1d 92 , the novel protein Spag6 (Sperm-associated antigen 6), which localizes to the ciliary axoneme and is essential for rotational polarity 93 , and c21orf59/Kurly, a novel cytoplasmic protein that physically interacts with the core PCP protein Dishevelled 94 .…”

Cilia distribution and polarity in the epithelial lining of the mouse middle ear cavity

“…In the respiratory epithelium of the trachea, motile cilia are aligned uniformly to generate a directional beating motion across the mucosal tissue for clearance212246. Although the polarity of the motile cilia in the nasal epithelium has not been examined directly, their motility and kinetics4748495051 suggest that cilia in the nasal respiratory epithelium are likely also aligned to generate synchronized beating waves for mucociliary clearance functions.…”

Myosin-I molecular motors at a glance

“…Myo1c, Myo1d and Myo1e have been found to contribute to the stability of cell-cell adhesion at adherens junctions, and Myo1e has been found at focal adhesions (Bi et al, 2013;Gupta et al, 2013;Hegan et al, 2015;Oh et al, 2013;Petzoldt et al, 2012;Spéder et al, 2006;Stöffler and Bähler, 1998;Stöffler et al, 1995;Tokuo and Coluccio, 2013). Myo1c localizes to E-cadherin-rich areas in cell-cell contacts between Madin-Darby canine kidney epithelial (MDCK) cells and contributes to the stability of these junctions, although it is unclear how Myo1c functionally establishes and/or maintains this stability (Tokuo and Coluccio, 2013).…”

“…Interestingly, mouse Myo1c has been shown to power asymmetric actin filament gliding in an in vitro motility assay, which has been provocatively suggested to be related to this organ-patterning asymmetry (Pyrpassopoulos et al, 2012). In rats, Myo1d function at adherens junctions influences the establishment and/or maintenance of rotational planar cell polarity in ciliated tracheal and ependymal epithelial cells, but does not do so in all tissues that exhibit planar cell polarity (Hegan et al, 2015). Myo1e localizes to sites of actin polymerization and adhesion in lamellipodia, thereby influencing adhesion formation and actin dynamics through localization of its binding partners (Gupta et al, 2013;Stöffler et al, 1995).…”