nNOS 调节小鼠气管中的纤毛细胞极性、纤毛摆动频率和定向流动。
nNOS regulates ciliated cell polarity, ciliary beat frequency, and directional flow in mouse trachea.
机构信息
Center for Developmental Genetics, Stony Brook University, Stony Brook, NY, USA.
Department of Anesthesiology, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA.
出版信息
Life Sci Alliance. 2021 Mar 2;4(5). doi: 10.26508/lsa.202000981. Print 2021 May.
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.
气道的清除依赖于跨黏液纤毛上皮的定向黏液流动，而流动不足与多种人类疾病有关。有效的流动依赖于多纤毛细胞的适当极化和足够的纤毛拍打频率。我们表明，NO 由小鼠气管中的多纤毛细胞中的 nNOS 产生，它控制着平面极性和纤毛拍打频率，因此对于产生强大的流动是必要的。nNOS 对纤毛细胞极性的影响依赖于它与肌动蛋白和微管的顶端网络的相互作用，并涉及 RhoA 激活。nNOS 对拍打频率的作用是通过鸟苷酸环化酶介导的；NO 供体和 cGMP 都可以增加气管中的流体流动，并挽救 nNOS 突变体中流动不足的问题。我们的结果将纤毛细胞中 NO 的不足与流动和纤毛活动的缺陷联系起来，这可能解释了纤毛病中呼出的 NO 水平较低的原因。
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