State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
College of Advanced Agricultural Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
J Mol Cell Biol. 2024 Jan 17;15(8). doi: 10.1093/jmcb/mjad050.
Microtubule networks support many cellular processes and exhibit a highly ordered architecture. However, due to the limited axial resolution of conventional light microscopy, the structural features of these networks cannot be resolved in three-dimensional (3D) space. Here, we used customized ultra-high-resolution interferometric single-molecule localization microscopy to characterize the microtubule networks in Caco2 cells. We found that the calmodulin-regulated spectrin-associated proteins (CAMSAPs) localize at a portion of microtubule intersections. Further investigation showed that depletion of CAMSAP2 and CAMSAP3 leads to the narrowing of the inter-microtubule distance. Mechanistically, CAMSAPs recognize microtubule defects, which often occur near microtubule intersections, and then recruit katanin to remove the damaged microtubules. Therefore, the CAMSAP-katanin complex is a regulatory module for the distance between microtubules. Taken together, our results characterize the architecture of cellular microtubule networks in high resolution and provide molecular insights into how the 3D structure of microtubule networks is controlled.
微管网络支持许多细胞过程，并表现出高度有序的结构。然而，由于传统的光显微镜的轴向分辨率有限，这些网络的结构特征无法在三维（3D）空间中得到解决。在这里，我们使用定制的超高分辨率干涉单分子定位显微镜来描述 Caco2 细胞中的微管网络。我们发现钙调蛋白调节的血影蛋白相关蛋白（CAMSAPs）定位于微管交叉的一部分。进一步的研究表明，CAMSAP2 和 CAMSAP3 的缺失会导致微管之间的距离变窄。从机制上讲，CAMSAPs 识别微管缺陷，这些缺陷通常发生在微管交叉附近，然后招募katanin 去除受损的微管。因此，CAMSAP-katanin 复合物是微管之间距离的调节模块。总之，我们的结果以高分辨率描述了细胞微管网络的结构，并提供了分子层面上的见解，了解微管网络的 3D 结构是如何被控制的。
