Multicilin promotes centriole assembly and ciliogenesis during multiciliate cell differentiation.
Multicilin promotes centriole assembly and ciliogenesis during multiciliate cell differentiation.
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DOI：
10.1038/ncb2406
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发表时间：
2012-01-08
影响因子：
21.3
通讯作者：
中科院分区：
文献类型：
--
作者：
多纤毛细胞在呼吸系统、脑室管膜和雌性生殖道中发挥重要作用，沿沿着上皮表面产生强有力的液体流动。这些特化的细胞在发育过程中形成，当上皮祖细胞经历一种不寻常的纤毛发生形式时，它们组装并投射数百根运动纤毛。Notch抑制多种上皮中多纤毛细胞的形成，但祖细胞如何克服侧向抑制并启动多纤毛细胞分化尚不清楚。在这里，我们确定了一个卷曲螺旋蛋白，称为multicilin，这是Notch调节和高度表达的发展中的上皮细胞的multicilate细胞的形式。抑制multicilin的功能，特别是块多纤毛细胞在非洲爪蟾皮肤和肾脏的形成，而异位表达诱导异位位置的多纤毛细胞的分化。Multicilin定位于细胞核，在那里它直接激活多纤毛细胞形成所需的基因的表达，包括FoxJ1和介导中心粒组装的基因。Multicilin也是促进小鼠气道上皮培养物中多纤毛细胞分化所必需和充分的。这些研究结果表明，multicilin启动多纤毛细胞分化在不同的组织，协调促进运动纤毛和中心粒组装所需的转录变化。
Multiciliate cells function prominently in the respiratory system, brain ependyma, and female reproductive tract to produce vigorous fluid flow along epithelial surfaces. These specialized cells form during development when epithelial progenitors undergo an unusual form of ciliogenesis, in which they assemble and project hundreds of motile cilia. Notch inhibits multiciliate cell formation in diverse epithelia, but how progenitors overcome lateral inhibition and initiate multiciliate cell differentiation is unknown. Here we identify a coiled-coil protein, termed multicilin, which is Notch regulated and highly expressed in developing epithelia where multiciliate cells form. Inhibiting multicilin function specifically blocks multiciliate cell formation in the Xenopus skin and kidney, while ectopic expression induces the differentiation of multiciliate cells in ectopic locations. Multicilin localizes to the nucleus, where it directly activates the expression of genes required for multiciliate cell formation, including FoxJ1 and genes mediating centriole assembly. Multicilin is also necessary and sufficient to promote multiciliate cell differentiation in mouse airway epithelial cultures. These findings suggest that multicilin initiates multiciliate cell differentiation in diverse tissues, by coordinately promoting the transcriptional changes required for motile ciliogenesis and centriole assembly.
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影响因子：
4.5
作者：
Ma, Ming;Jiang, Yun-Jin
通讯作者：
Jiang, Yun-Jin
影响因子：
64.8
作者：
Dzhindzhev, Nikola S.;Yu, Quan D.;Glover, David M.
通讯作者：
Glover, David M.
影响因子：
21.3
作者：
Habedanck, R;Stierhof, YD;Nigg, EA
通讯作者：
Nigg, EA
影响因子：
4.3
作者：
Seo, Seongjin;Kroll, Kristen L.
通讯作者：
Kroll, Kristen L.
DOI：
10.1083/jcb.201007107
发表时间：
2010-11-15
期刊：
The Journal of cell biology
影响因子：
--
作者：
Cizmecioglu O;Arnold M;Bahtz R;Settele F;Ehret L;Haselmann-Weiss U;Antony C;Hoffmann I
通讯作者：
Hoffmann I