The atypical cadherin Dachsous1 localizes to the base of the ciliary apparatus in airway epithelia

The atypical cadherin Dachsous1 localizes to the base of the ciliary apparatus in airway epithelia
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DOI:
10.1016/j.bbrc.2016.04.036
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发表时间:
2016-05-13
影响因子:
3.1
通讯作者:
Braun, Gerald S.
Braun, Gerald S.
中科院分区:
生物学4区
文献类型:
--
作者:
Dau, Cecile;Fliegauf, Manfred;Braun, Gerald S.

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粘膜纤毛清除需要气道纤毛的明确方向和协调运动,这是通过平面细胞极性信号(PCP)建立的。非典型钙粘蛋白Dachsous1(Dchs1)是一种跨膜蛋白,在D.黑腹菌然而,很少有人知道Dchs1的表达和其潜在的作用,PCP在哺乳动物成年组织。在这里,我们发现Dchs1在小鼠胚胎中普遍表达,但在成年阶段的肺组织中表现出高度限制的表达。引人注目的是,人Dchs1只定位于培养的人呼吸道上皮细胞与分化的运动9 + 2纤毛的纤毛器的基础。这种定位可能在功能上是重要的,因为我们观察到异常DCHS1 mRNA在人非小细胞肺癌组织中的表达。总之,我们建立Dchs1作为睫状体基底周围的膜结构域的一个组成部分。这表明Dchs1在PCP依赖的纤毛功能组织中的特定作用以及在肺部疾病中的可能作用。(C)2016 Elsevier Inc. All rights reserved.
Mucociliary clearance requires the distinct orientation and coordinated movement of airway cilia, which is established through planar cell polarity signaling (PCP). The atypical cadherin Dachsous1 (Dchs1) is a transmembrane protein that regulates PCP in D. melanogaster. However, little is known about Dchs1 expression and its potential role in PCP in mammalian adult tissues. Here, we show that Dchs1 is ubiquitously expressed in mouse embryos, but exhibits a highly restricted expression to lung tissues in the adult stage. Strikingly, human Dchs1 localized exclusively to the base of the ciliary apparatus in cultured human respiratory epithelial cells with differentiated motile 9 + 2 cilia. This localization could be functionally important as we observed aberrant DCHS1 mRNA expression in human non-small cell lung cancer tissue. In sum, we establish Dchs1 as a component of the membrane domain surrounding the ciliary base. This suggests a specific role of Dchs1 in PCP-dependent organization of ciliary function and a possible role in lung disease. (C) 2016 Elsevier Inc. All rights reserved.