Department of Biological Sciences, University of Cyprus, Nicosia 2109, Cyprus.
Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK; Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK.
Cell Rep. 2022 Jul 19;40(3):111091. doi: 10.1016/j.celrep.2022.111091.
Cadherins and integrins are intrinsically linked through the actin cytoskeleton and are largely responsible for the mechanical integrity and organization of tissues. We show that cadherin clustering stimulates and spatially guides integrin activation. Adherens junction (AJ)-associated integrin activation depends on locally generated tension and does not require extracellular matrix ligands. It leads to the creation of primed integrin clusters, which spatially determine where focal adhesions will form if ligands are present and where ligands will be deposited. AJs that display integrin activation are targeted by microtubules facilitating their disassembly via caveolin-based endocytosis, showing that integrin activation impacts the stability of the core cadherin complex. Thus, the interplay between cadherins and integrins is more intimate than what was once believed and is rooted in the capacity of active integrins to be stabilized via AJ-generated tension. Altogether, our data establish a mechanism of cross-regulation between cadherins and integrins.
钙黏蛋白和整合素通过肌动蛋白细胞骨架内在地联系在一起，在很大程度上负责组织的机械完整性和组织。我们表明，钙黏蛋白聚集刺激并在空间上指导整合素的激活。粘着连接（AJ）相关整合素的激活取决于局部产生的张力，并不需要细胞外基质配体。它导致形成被激活的整合素簇，这些簇在空间上决定了如果存在配体，焦点黏附将在哪里形成，以及配体将在哪里沉积。显示整合素激活的 AJ 被微管靶向，通过基于窖蛋白的内吞作用促进其解体，表明整合素激活影响核心钙黏蛋白复合物的稳定性。因此，钙黏蛋白和整合素之间的相互作用比以前认为的更为密切，其根源在于活性整合素能够通过 AJ 产生的张力稳定。总之，我们的数据建立了钙黏蛋白和整合素之间的交叉调节机制。
