CRB3 navigates Rab11 trafficking vesicles to promote γTuRC assembly during ciliogenesis
CRB3 navigates Rab11 trafficking vesicles to promote γTuRC assembly during ciliogenesis
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CRB3 导航 Rab11 运输囊泡以促进纤毛发生过程中的 γTuRC 组装
DOI：
10.1101/2023.02.15.528649
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发表时间：
2023-09
期刊：
影响因子：
7.7
通讯作者：
Zhang M
中科院分区：
文献类型：
--
作者：
Wang B;Liang Z;Tan T;Li Juan;Ren Yu;Zhang M
初级纤毛在调节细胞分化、信号转导和组织结构等方面起着重要作用。初级纤毛功能障碍可导致纤毛疾病和癌症。初级纤毛的形成和组织与细胞极性蛋白高度相关，如顶极蛋白CRB3。然而，CRB3调控纤毛发生的分子机制和CRB3的位置仍不清楚。在这里，我们表明，CRB3，作为一个导航器，在纤毛发生过程中调节γ-TURC组装中的囊泡运输，以及在肿瘤发生中调节纤毛相关的HH和WNT信号通路。Crb3基因敲除小鼠表现出乳腺导管管腔和肾小管初级纤毛的严重缺陷，而乳腺上皮特异的Crb3基因敲除小鼠则表现出促进导管上皮细胞增殖和肿瘤发生的作用。CRB3在乳腺上皮的管腔形成和纤毛组装中是必不可少的。我们证明了CRB3定位于基底体，并且CRB3的转运是由Rab11阳性的内体介导的。值得注意的是，CRB3与Rab11相互作用，将GCP6/Rab11运输小泡导航到CEP290，导致完整的γ-TURC组装。此外，CRB3缺失的细胞对HH信号通路的激活没有反应，而CRB3调节Wnt信号通路。因此，我们的研究揭示了CRB3识别Rab11阳性内体促进纤毛发生的分子机制，并在肿瘤发生中调节纤毛相关的信号通路。
The primary cilium plays important roles in regulating cell differentiation, signal transduction, and tissue organization. Dysfunction of the primary cilium can lead to ciliopathies and cancer. The formation and organization of the primary cilium are highly associated with cell polarity proteins, such as the apical polarity protein CRB3. However, the molecular mechanisms by which CRB3 regulates ciliogenesis and the location of CRB3 remain unknown. Here, we show that CRB3, as a navigator, regulates vesicle trafficking in γ-TuRC assembly during ciliogenesis and cilium-related Hh and Wnt signaling pathways in tumorigenesis. Crb3 knockout mice display severe defects of the primary cilium in the mammary ductal lumen and renal tubule, while mammary epithelial-specific Crb3 knockout mice exhibit the promotion of ductal epithelial hyperplasia and tumorigenesis. CRB3 is essential for lumen formation and ciliary assembly in the mammary epithelium. We demonstrate that CRB3 localizes to the basal body and that CRB3 trafficking is mediated by Rab11-positive endosomes. Significantly, CRB3 interacts with Rab11 to navigate GCP6/Rab11 trafficking vesicles to CEP290, resulting in intact γ-TuRC assembly. In addition, CRB3-depleted cells are unresponsive to the activation of the Hh signaling pathway, while CRB3 regulates the Wnt signaling pathway. Therefore, our studies reveal the molecular mechanisms by which CRB3 recognizes Rab11-positive endosomes to facilitate ciliogenesis, and regulates cilium-related signaling pathways in tumorigenesis.
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影响因子：
5.5
作者：
Wheway G;Nazlamova L;Hancock JT
通讯作者：
Hancock JT
影响因子：
7.5
作者：
Liu, Peng;Wuertz, Martin;Schiebel, Elmar
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DOI：
10.4103/jomfp.jomfp_48_17
发表时间：
2017-01
期刊：
Journal of oral and maxillofacial pathology : JOMFP
影响因子：
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作者：
Venkatesh D
通讯作者：
Venkatesh D
影响因子：
3.7
作者：
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影响因子：
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作者：
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通讯作者：
McDermott KM