Membrane architecture and adherens junctions contribute to strong Notch pathway activation.
Membrane architecture and adherens junctions contribute to strong Notch pathway activation.
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DOI：
10.1242/dev.199831
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发表时间：
2021-10-01
期刊：
影响因子：
--
通讯作者：
Bray SJ
中科院分区：
文献类型：
--
作者：
Falo-Sanjuan J;Bray SJ
Notch通路在多种组织、发育阶段和生物体中介导细胞间的通讯。通路的激活依赖于跨膜配体和相邻细胞上的受体之间的相互作用。因此，途径的活性可能受到膜之间接触的大小、组成或动力学的影响。在果蝇胚胎中，Notch信号的起始发生在细胞化过程中，此时侧细胞膜和贴壁连接首次沉积，这使得我们能够研究膜结构和特定的连接结构域对信号传递的重要性。通过测量活胚胎中Notch依赖的转录，我们确定它是在侧膜生长时启动的，并且信号的启动与其形成的特定阶段相关。然而，侧膜本身的长度并不是有限的。相反，与膜沉积同时组装的贴壁连接促成了转录所需的高水平信号传递，正如α-连环蛋白耗尽的后果所表明的那样。综上所述，这些结果表明，侧膜接触的建立对Notch的反式激活可能是有限的，并表明粘附性连接在调节Notch活性中发挥着重要作用。摘要：在活体胚胎中测量Notch依赖的转录表明，与侧膜相关的特征是启动Notch信号所必需的。扰乱膜的生长或粘连连接会阻止正常的激活。
The Notch pathway mediates cell-to-cell communication in a variety of tissues, developmental stages and organisms. Pathway activation relies on the interaction between transmembrane ligands and receptors on adjacent cells. As such, pathway activity could be influenced by the size, composition or dynamics of contacts between membranes. The initiation of Notch signalling in the Drosophila embryo occurs during cellularization, when lateral cell membranes and adherens junctions are first being deposited, allowing us to investigate the importance of membrane architecture and specific junctional domains for signalling. By measuring Notch-dependent transcription in live embryos, we established that it initiates while lateral membranes are growing and that signalling onset correlates with a specific phase in their formation. However, the length of the lateral membranes per se was not limiting. Rather, the adherens junctions, which assemble concurrently with membrane deposition, contributed to the high levels of signalling required for transcription, as indicated by the consequences of α-Catenin depletion. Together, these results demonstrate that the establishment of lateral membrane contacts can be limiting for Notch trans-activation and suggest that adherens junctions play an important role in modulating Notch activity. Summary: Measuring Notch-dependent transcription in live embryos reveals that features associated with lateral membranes are required for initiation of Notch signalling. Perturbing membrane growth or adherens junctions prevents normal activation.
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影响因子：
11.8
作者：
Gomez-Lamarca MJ;Falo-Sanjuan J;Stojnic R;Abdul Rehman S;Muresan L;Jones ML;Pillidge Z;Cerda-Moya G;Yuan Z;Baloul S;Valenti P;Bystricky K;Payre F;O'Holleran K;Kovall R;Bray SJ
通讯作者：
Bray SJ
影响因子：
16.6
作者：
Fabrowski, Piotr;Necakov, Aleksandar S.;Mumbauer, Simone;Loeser, Eva;Reversi, Alessandra;Streichan, Sebastian;Briggs, John A. G.;De Renzis, Stefano
通讯作者：
De Renzis, Stefano
影响因子：
10.6
作者：
Chan, TF;Vese, LA
通讯作者：
Vese, LA
影响因子：
9.2
作者：
Brandt, A;Papagiannouli, F;Grosshans, J
通讯作者：
Grosshans, J
影响因子：
64.8
作者：
Coumailleau, F.;Fuerthauer, M.;Gonzalez-Gaitan, M.
通讯作者：
Gonzalez-Gaitan, M.