State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences 201210 Shanghai, China.
National Center for Protein Science Shanghai, Shanghai Institute of Biochemistry and Cell Biology, CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, 201210 Shanghai, China.
Proc Natl Acad Sci U S A. 2018 Sep 11;115(37):9246-9251. doi: 10.1073/pnas.1801810115. Epub 2018 Aug 27.
Cell-cell adhesion is important for cell growth, tissue development, and neural network formation. Structures of cell adhesion molecules have been widely studied by crystallography, revealing the molecular details of adhesion interfaces. However, due to technical limitations, the overall structure and organization of adhesion molecules at cell adhesion interfaces has not been fully investigated. Here, we combine electron microscopy and other biophysical methods to characterize the structure of cell-cell adhesion mediated by the cell adhesion molecule Sidekick (Sidekick-1 and Sidekick-2) and obtain 3D views of the Sidekick-mediated adhesion interfaces as well as the organization of Sidekick molecules between cell membranes by electron tomography. The results suggest that the Ig-like domains and the fibronectin III (FnIII) domains of Sidekicks play different roles in cell adhesion. The Ig-like domains mediate the homophilic transinteractions bridging adjacent cells, while the FnIII domains interact with membranes, resulting in a tight adhesion interface between cells that may contribute to the specificity and plasticity of cell-cell contacts during cell growth and neural development.
细胞间黏附对于细胞生长、组织发育和神经网络形成非常重要。通过晶体学广泛研究了细胞黏附分子的结构，揭示了黏附界面的分子细节。然而，由于技术限制，细胞黏附界面处黏附分子的整体结构和组织尚未得到充分研究。在这里，我们结合电子显微镜和其他生物物理方法来表征由细胞黏附分子 Sidekick（Sidekick-1 和 Sidekick-2）介导的细胞-细胞黏附，并通过电子断层扫描获得 Sidekick 介导的黏附界面的 3D 视图以及细胞膜之间 Sidekick 分子的组织。结果表明，Sidekicks 的免疫球蛋白样结构域和纤维连接蛋白 III（FnIII）结构域在细胞黏附中发挥不同的作用。免疫球蛋白样结构域介导桥接相邻细胞的同种型相互作用，而 FnIII 结构域与膜相互作用，导致细胞之间的紧密黏附界面，这可能有助于细胞生长和神经发育过程中细胞接触的特异性和可塑性。
