Sturgess Wesley, Packirisamy Swathi, Geneidy Rodina, Nordenfelt Pontus, Swaminathan Vinay
Division of Oncology, Department of Clinical Sciences, Lund University, Lund, Sweden.
Wallenberg Centre for Molecular Medicine, Lund University, Lund, Sweden.
iScience. 2024 Nov 9;27(12):111355. doi: 10.1016/j.isci.2024.111355. eCollection 2024 Dec 20.
Fibroblasts are adherent cells that maintain tissue homeostasis by sensing and responding to the extracellular matrix (ECM). Focal adhesions (FAs) link these ECM changes to actomyosin dynamics through changes in its composition, influencing cellular response. Septin-7 (Sept-7) has previously been found in FA proteomics studies and shown to influence ECM sensing. Using total internal reflection microscopy, we found that ECM-mediated integrin activation regulates spatially distinct Sept-7 structures in FAs. In perinuclear regions, ECM binding stabilized Sept-7 bundles at the back of FAs, while in the core of peripheral FAs high integrin activation promoted elongation of Sept-7 structures. Ventral Sept-7 structures were crucial for ECM sensing, impacting region-specific FA elongation, stabilization, and contributing to fibroblast mechanosensitivity. Taken together, our results suggest that ECM and integrin-dependent regulation of ventral Sept-7 structures plays a pivotal role in fibroblast ECM sensing and mechanotransduction through its recruitment and assembly into FA subpopulations.
成纤维细胞是通过感知和响应细胞外基质（ECM）来维持组织稳态的贴壁细胞。黏着斑（FAs）通过其组成变化将这些ECM变化与肌动球蛋白动力学联系起来，影响细胞反应。在之前的FA蛋白质组学研究中发现了Septin-7（Sept-7），并表明其影响ECM感知。使用全内反射显微镜，我们发现ECM介导的整合素激活调节了FAs中空间上不同的Sept-7结构。在核周区域，ECM结合稳定了FAs后部的Sept-7束，而在外周FAs的核心，高整合素激活促进了Sept-7结构的伸长。腹侧Sept-7结构对于ECM感知至关重要，影响区域特异性FA的伸长、稳定，并有助于成纤维细胞的机械敏感性。综上所述，我们的结果表明，腹侧Sept-7结构的ECM和整合素依赖性调节通过其募集和组装到FA亚群中，在成纤维细胞ECM感知和机械转导中起关键作用。
