TY - JOUR T1 - nNOS regulates ciliated cell polarity, ciliary beat frequency, and directional flow in mouse trachea JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.202000981 VL - 4 IS - 5 SP - e202000981 AU - Anatoly Mikhailik AU - Tatyana V Michurina AU - Krikor Dikranian AU - Stephen Hearn AU - Vladimir I Maxakov AU - Saul S Siller AU - Ken-Ichi Takemaru AU - Grigori Enikolopov AU - Natalia Peunova Y1 - 2021/05/01 UR - https://www.life-science-alliance.org/content/4/5/e202000981.abstract N2 - Clearance of the airway is dependent on directional mucus flow across the mucociliary epithelium, and deficient flow is implicated in a range of human disorders. Efficient flow relies on proper polarization of the multiciliated cells and sufficient ciliary beat frequency. We show that NO, produced by nNOS in the multiciliated cells of the mouse trachea, controls both the planar polarity and the ciliary beat frequency and is thereby necessary for the generation of the robust flow. The effect of nNOS on the polarity of ciliated cells relies on its interactions with the apical networks of actin and microtubules and involves RhoA activation. The action of nNOS on the beat frequency is mediated by guanylate cyclase; both NO donors and cGMP can augment fluid flow in the trachea and rescue the deficient flow in nNOS mutants. Our results link insufficient availability of NO in ciliated cells to defects in flow and ciliary activity and may thereby explain the low levels of exhaled NO in ciliopathies. ER -