RT Journal Article
SR Electronic
T1 nNOS regulates ciliated cell polarity, ciliary beat frequency, and directional flow in mouse trachea
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202000981
DO 10.26508/lsa.202000981
VO 4
IS 5
A1 Anatoly Mikhailik
A1 Tatyana V Michurina
A1 Krikor Dikranian
A1 Stephen Hearn
A1 Vladimir I Maxakov
A1 Saul S Siller
A1 Ken-Ichi Takemaru
A1 Grigori Enikolopov
A1 Natalia Peunova
YR 2021
UL https://www.life-science-alliance.org/content/4/5/e202000981.abstract
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.