PT  - JOURNAL ARTICLE
AU  - Mikhailik, Anatoly
AU  - Michurina, Tatyana V
AU  - Dikranian, Krikor
AU  - Hearn, Stephen
AU  - Maxakov, Vladimir I
AU  - Siller, Saul S
AU  - Takemaru, Ken-Ichi
AU  - Enikolopov, Grigori
AU  - Peunova, Natalia
TI  - nNOS regulates ciliated cell polarity, ciliary beat frequency, and directional flow in mouse trachea
AID  - 10.26508/lsa.202000981
DP  - 2021 May 01
TA  - Life Science Alliance
PG  - e202000981
VI  - 4
IP  - 5
4099  - http://www.life-science-alliance.org/content/4/5/e202000981.short
4100  - http://www.life-science-alliance.org/content/4/5/e202000981.full
SO  - Life Sci. Alliance2021 May 01; 4
AB  - 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.