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作为Wnt信号细胞器的纤毛

Cilia as Wnt signaling organelles.

作者信息

Niehrs Christof, Da Silva Fabio, Seidl Carina

机构信息

Division of Molecular Embryology, DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany; Institute of Molecular Biology (IMB), 55128 Mainz, Germany.

Division of Molecular Embryology, DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany.

出版信息

Trends Cell Biol. 2025 Jan;35(1):24-32. doi: 10.1016/j.tcb.2024.04.001. Epub 2024 May 1.

Abstract

Cilia and Wnt signaling have a complex relationship, wherein Wnt regulates cilia and, conversely, cilia may affect Wnt signaling. Recently, it was shown that Wnt receptors are present in flagella, primary cilia, and multicilia, where they transmit an intraciliary signal that is independent of β-catenin. Intraciliary Wnt signaling promotes ciliogenesis, affecting male fertility, adipogenesis, and mucociliary clearance. Wnt also stimulates the beating of motile cilia, highlighting that these nanomotors, too, are chemosensory. Intraciliary Wnt signaling employs a Wnt-protein phosphatase 1 (PP1) signaling axis, involving the canonical Wnt pathway's inhibition of glycogen synthase kinase 3 (GSK3) to repress PP1 activity. Collectively, these findings support that cilia are Wnt signaling organelles, with implications for ciliopathies and cancer.

摘要

纤毛与Wnt信号传导存在复杂的关系,其中Wnt调节纤毛,反之,纤毛可能影响Wnt信号传导。最近的研究表明,Wnt受体存在于鞭毛、初级纤毛和多纤毛中,在这些部位它们传递一种独立于β-连环蛋白的纤毛内信号。纤毛内的Wnt信号传导促进纤毛生成,影响男性生育能力、脂肪生成和黏液纤毛清除功能。Wnt还刺激运动性纤毛的摆动,这突出表明这些纳米马达同样具有化学感应功能。纤毛内的Wnt信号传导利用Wnt-蛋白磷酸酶1(PP1)信号轴,涉及经典Wnt途径对糖原合酶激酶3(GSK3)的抑制,从而抑制PP1活性。总体而言,这些发现支持纤毛是Wnt信号传导细胞器,这对纤毛病和癌症具有重要意义。

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