Cells have evolved mechanisms to sense the composition of their adhesive microenvironment. Although much is known about general mechanisms employed by adhesion receptors to relay signals between the extracellular environment and the cytoskeleton, the nuances of ligand-specific signalling remain undefined. Here, we investigated how glomerular podocytes, and four other basement membrane-associated cell types, respond morphologically to different basement membrane ligands. We defined the composition of the respective adhesion complexes using mass spectrometry-based proteomics. On type IV collagen, all epithelial cell types adopted a round morphology, with a single lamellipodium and large adhesion complexes rich in actin-binding proteins. On laminin (511 or 521), all cell types attached to a similar degree but were polygonal in shape with small adhesion complexes enriched in endocytic and microtubule-binding proteins. Consistent with their distinctive morphologies, cells on type IV collagen exhibited high Rac1 activity, while those on laminin had elevated PKCα. Perturbation of PKCα was able to interchange morphology consistent with a key role for this pathway in matrix ligand-specific signalling. Therefore, this study defines the switchable basement membrane adhesome and highlights two key signalling pathways within the systems that determine distinct cell morphologies. Proteomic data are available via ProteomeXchange with identifier PXD017913.

细胞已经进化出机制来感知其粘附微环境的组成。尽管对粘附受体在细胞外环境和细胞骨架之间传递信号的一般机制了解很多，但配体特异性信号传导的细微差别仍未确定。在这里，我们研究了肾小球足细胞和其他四种基底膜相关细胞类型如何在形态学上对不同的基底膜配体作出反应。我们使用基于质谱的蛋白质组学定义了各自粘附复合物的组成。在 IV 型胶原蛋白上，所有上皮细胞类型均采用圆形形态，具有单个薄片和富含肌动蛋白结合蛋白的大粘附复合物。在层粘连蛋白（511 或 521）上，所有细胞类型的附着程度相似，但呈多边形，具有富含内吞蛋白和微管结合蛋白的小粘附复合物。与其独特的形态一致，IV 型胶原蛋白上的细胞表现出高 Rac1 活性，而层粘连蛋白上的细胞具有升高的 PKCα。PKCα 的扰动能够交换与该途径在基质配体特异性信号传导中的关键作用一致的形态。因此，本研究定义了可切换的基底膜粘附体，并强调了系统内决定不同细胞形态的两个关键信号通路。PKCα 的扰动能够交换与该途径在基质配体特异性信号传导中的关键作用一致的形态。因此，本研究定义了可切换的基底膜粘附体，并强调了系统内决定不同细胞形态的两个关键信号通路。PKCα 的扰动能够交换与该途径在基质配体特异性信号传导中的关键作用一致的形态。因此，本研究定义了可切换的基底膜粘附体，并强调了系统内决定不同细胞形态的两个关键信号通路。蛋白质组学数据可 通过 ProteomeXchange 获得，标识符为 PXD017913。