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Wnt 和谷氨酸受体协调干细胞动力学和不对称细胞分裂。

Wnt- and glutamate-receptors orchestrate stem cell dynamics and asymmetric cell division.

机构信息

Centre for Stem Cells and Regenerative Medicine, King's College London, London, United Kingdom.

出版信息

Elife. 2021 May 24;10:e59791. doi: 10.7554/eLife.59791.

DOI:10.7554/eLife.59791
PMID:34028355
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8177892/
Abstract

The Wnt-pathway is part of a signalling network that regulates many aspects of cell biology. Recently, we discovered crosstalk between AMPA/Kainate-type ionotropic glutamate receptors (iGluRs) and the Wnt-pathway during the initial Wnt3a-interaction at the cytonemes of mouse embryonic stem cells (ESCs). Here, we demonstrate that this crosstalk persists throughout the Wnt3a-response in ESCs. Both AMPA and Kainate receptors regulate early Wnt3a-recruitment, dynamics on the cell membrane, and orientation of the spindle towards a Wnt3a-source at mitosis. AMPA receptors specifically are required for segregating cell fate components during Wnt3a-mediated asymmetric cell division (ACD). Using Wnt-pathway component knockout lines, we determine that Wnt co-receptor Lrp6 has particular functionality over Lrp5 in cytoneme formation, and in facilitating ACD. Both Lrp5 and 6, alongside pathway effector β-catenin act in concert to mediate the positioning of the dynamic interaction with, and spindle orientation to, a localised Wnt3a-source. Wnt-iGluR crosstalk may prove pervasive throughout embryonic and adult stem cell signalling.

摘要

Wnt 信号通路是细胞生物学中调节许多方面的信号网络的一部分。最近，我们在小鼠胚胎干细胞 (ESC) 的轴突小体中发现了 AMPA/KA 型离子型谷氨酸受体 (iGluR) 与 Wnt 通路之间的串扰，这是 Wnt3a 相互作用的初始阶段。在这里，我们证明这种串扰在整个 Wnt3a 反应中都存在。AMPA 和 Kainate 受体都调节早期 Wnt3a 的募集、细胞膜上的动力学以及有丝分裂时纺锤体向 Wnt3a 来源的方向。AMPA 受体在 Wnt3a 介导的不对称细胞分裂 (ACD) 中对细胞命运成分的分离是特异性的。使用 Wnt 信号通路成分敲除系，我们确定 Wnt 共受体 Lrp6 在轴突小体形成中具有比 Lrp5 更特殊的功能，并促进 ACD。Lrp5 和 6 以及途径效应物 β-连环蛋白协同作用，共同介导与局部 Wnt3a 源的动态相互作用和纺锤体的定向。Wnt-iGluR 串扰可能在整个胚胎和成体干细胞信号中普遍存在。

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