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平面细胞极性信号通路介导的细胞自主极化

Cell autonomous polarization by the planar cell polarity signaling pathway.

作者信息

Weiner Alexis T, Nissen Silas Boye, Suyama Kaye, Cho Bomsoo, Pierre-Louis Gandhy, Axelrod Jeffrey D

机构信息

Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.

The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), University of Copenhagen, Copenhagen, Denmark.

出版信息

bioRxiv. 2025 Jan 26:2023.09.26.559449. doi: 10.1101/2023.09.26.559449.

Abstract

Planar Cell Polarity (PCP) signaling polarizes epithelial cells in a plane orthogonal to their apical-basal axis. A core PCP signaling module segregates two distinct molecular subcomplexes to opposite sides of cells and coordinates the direction of polarization between neighboring cells. Homodimers of the atypical cadherin Flamingo are thought to scaffold these subcomplexes and are required for intercellular polarity signaling. Feedback is required for polarization, but whether feedback requires intercellular and/or intracellular pathways is unknown, and traditional genetic tools have limited utility in dissecting these mechanisms. Using novel tools, we show that cells lacking Flamingo, or bearing a homodimerization-deficient Flamingo, do polarize, indicating that functional PCP subcomplexes form and segregate cell-autonomously. We identify feedback pathways and propose a competitive binding-based asymmetry amplifying mechanism that each operate cell-autonomously. The intrinsic logic of PCP signaling is therefore more similar to that in single cell polarizing systems than was previously recognized.

摘要

平面细胞极性(PCP)信号通路在与上皮细胞顶-基轴正交的平面上使上皮细胞极化。一个核心PCP信号模块将两个不同的分子亚复合物分隔到细胞的相对两侧,并协调相邻细胞之间的极化方向。非典型钙黏蛋白Flamingo的同源二聚体被认为是这些亚复合物的支架,并且是细胞间极性信号传导所必需的。极化需要反馈,但反馈是否需要细胞间和/或细胞内途径尚不清楚,并且传统的遗传工具在剖析这些机制方面的效用有限。使用新型工具,我们表明缺乏Flamingo或携带同源二聚化缺陷型Flamingo的细胞确实会极化,这表明功能性PCP亚复合物自主形成并分离。我们确定了反馈途径,并提出了一种基于竞争性结合的不对称放大机制,每种机制都自主运作。因此,PCP信号传导的内在逻辑比以前认识到的更类似于单细胞极化系统中的逻辑。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b15/11781486/f4b031486901/nihpp-2023.09.26.559449v2-f0001.jpg

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