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; nonautonomous 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 and are polarized nearly simultaneously, and that 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.
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; nonautonomous 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 and are polarized nearly simultaneously, and that 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.
Authors: Mireille Montcouquiol; Rivka A Rachel; Pamela J Lanford; Neal G Copeland; Nancy A Jenkins; Matthew W Kelley Journal: Nature Date: 2003-04-30 Impact factor: 49.962