nNOS regulates ciliated cell polarity, ciliary beat frequency, and directional flow in mouse trachea

Mikhailik, Anatoly, Michurina, Tatyana V, Dikranian, Krikor, Hearn, Stephen, Maxakov, Vladimir I, Siller, Saul S, Takemaru, Ken-Ichi, Enikolopov, Grigori, Peunova, Natalia (May 2021) nNOS regulates ciliated cell polarity, ciliary beat frequency, and directional flow in mouse trachea. Life science alliance, 4 (5). ISSN 2575-1077

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Abstract

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.

Item Type:	Paper
Subjects:	bioinformatics bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics Investigative techniques and equipment > optical devices bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification organism description > animal organs, tissues, organelles, cell types and functions > cell types and functions > cell functions organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell polarity organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cell organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cell organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cell organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cells organism description > animal > mammal Investigative techniques and equipment > optical devices > microscope techniques or equipment organism description > animal > mammal > rodent > mouse bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > nitric oxide synthase organs, tissues, organelles, cell types and functions bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types organism description > animal > mammal > rodent
CSHL Authors:	Hearn, Stephen A.
Depositing User:	Sasha Luks-Morgan
Date:	May 2021
Date Deposited:	17 Jun 2021 12:20
Last Modified:	25 Jan 2024 15:25
PMCID:	PMC8008965
Related URLs:	PubMed
URI:	https://repository.cshl.edu/id/eprint/40219

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