Univ Rennes, CNRS, IGDR (Institut de Génétique et Développement de Rennes) - UMR 6290, F- 35000, Rennes, France.
Equipe Labellisée Ligue Nationale contre le cancer, Glasgow, United Kingdom.
Elife. 2021 Oct 1;10:e66659. doi: 10.7554/eLife.66659.
In multiple cell lineages, Delta-Notch signalling regulates cell fate decisions owing to unidirectional signalling between daughter cells. In pupal sensory organ lineage, Notch regulates the intra-lineage pIIa/pIIb fate decision at cytokinesis. Notch and Delta that localise apically and basally at the pIIa-pIIb interface are expressed at low levels and their residence time at the plasma membrane is in the order of minutes. How Delta can effectively interact with Notch to trigger signalling from a large plasma membrane area remains poorly understood. Here, we report that the signalling interface possesses a unique apico-basal polarity with Par3/Bazooka localising in the form of nano-clusters at the apical and basal level. Notch is preferentially targeted to the pIIa-pIIb interface, where it co-clusters with Bazooka and its cofactor Sanpodo. Clusters whose assembly relies on Bazooka and Sanpodo activities are also positive for Neuralized, the E3 ligase required for Delta activity. We propose that the nano-clusters act as snap buttons at the new pIIa-pIIb interface to allow efficient intra-lineage signalling.
在多个细胞谱系中,Delta-Notch 信号通过子细胞之间的单向信号传导调节细胞命运决定。在蛹感觉器官谱系中,Notch 在胞质分裂时调节细胞内的 pIIa/pIIb 命运决定。在 pIIa-pIIb 界面处定位于顶端和基底的 Notch 和 Delta 表达水平较低,其在质膜上的停留时间为数分钟。Delta 如何能够有效地与 Notch 相互作用,从而从大面积的质膜区域触发信号传导,这仍然知之甚少。在这里,我们报告说,信号界面具有独特的顶端-基底极性,Par3/Bazooka 以纳米簇的形式定位于顶端和基底水平。Notch 优先靶向 pIIa-pIIb 界面,在该处与 Bazooka 及其共因子 Sanpodo 共聚类。依赖 Bazooka 和 Sanpodo 活性组装的簇也对 Neuralized 呈阳性,Neuralized 是 Delta 活性所必需的 E3 连接酶。我们提出纳米簇作为新的 pIIa-pIIb 界面上的快速按钮,以允许有效的细胞内信号传导。