Cross-Scale Integrin Regulation Organizes ECM and Tissue Topology
Cross-Scale Integrin Regulation Organizes ECM and Tissue Topology
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DOI：
10.1016/j.devcel.2015.05.005
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发表时间：
2015-07-06
影响因子：
11.8
通讯作者：
Holley, Scott A.
中科院分区：
文献类型：
--
作者：
Juelich, Doerthe;Cobb, Garrett;Holley, Scott A.
动物组织的不同形态是由不同构型的粘附细胞和细胞外基质（ECM）构成的。在这里，我们阐明了一个跨尺度的机制，组织组装和ECM重塑涉及钙粘蛋白2，ECM蛋白纤连蛋白，及其受体整合素α 5。荧光互相关光谱内斑马鱼近轴中胚层间充质揭示了整合素α 5之间的物理关联相邻的细胞膜。这种整合素-整合素复合物与构象上无活性的整合素相关。钙粘蛋白2稳定整联蛋白缔合和失活整联蛋白构象。因此，组织的粘附间充质内部内的整合素抑制使纤连蛋白原纤维形成偏向于缺乏细胞-细胞粘附的组织表面。沿着新生体节边界，钙粘蛋白2水平降低，与整联蛋白α 5水平反相关。同时，整合素α 5聚集并采用活性构象，然后开始ECM组装。整联蛋白激活的这种跨尺度调节组织了脊椎动物体伸长和分割所需的ECM的定型模式。
The diverse morphologies of animal tissues are underlain by different configurations of adherent cells and extracellular matrix (ECM). Here, we elucidate a cross-scale mechanism for tissue assembly and ECM remodeling involving Cadherin 2, the ECM protein Fibronectin, and its receptor Integrin alpha 5. Fluorescence cross-correlation spectroscopy within the zebrafish paraxial mesoderm mesenchyme reveals a physical association between Integrin alpha 5 on adjacent cellmembranes. This Integrin-Integrin complex correlates with conformationally inactive Integrin. Cadherin 2 stabilizes both the Integrin association and inactive Integrin conformation. Thus, Integrin repression within the adherent mesenchymal interior of the tissue biases Fibronectin fibrillogenesis to the tissue surface lacking cell-cell adhesions. Along nascent somite boundaries, Cadherin 2 levels decrease, becoming anti-correlated with levels of Integrin alpha 5. Simultaneously, Integrin alpha 5 clusters and adopts the active conformation and then commences ECM assembly. This cross-scale regulation of Integrin activation organizes a stereotypic pattern of ECM necessary for vertebrate body elongation and segmentation.