Structural Biochemistry, Department of Chemistry, Bijvoet Centre for Biomolecular Research, Utrecht University, Utrecht, Netherlands.
Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, Utrecht, Netherlands.
J Cell Biol. 2025 Jan 6;224(1). doi: 10.1083/jcb.202206143. Epub 2024 Oct 10.
Microtubules are crucial in cells and are regulated by various mechanisms like posttranslational modifications, microtubule-associated proteins, and tubulin isoforms. Recently, the conformation of the microtubule lattice has also emerged as a potential regulatory factor, but it has remained unclear to what extent different lattices co-exist within the cell. Using cryo-electron tomography, we find that, while most microtubules have a compacted lattice (∼41 Å monomer spacing), approximately a quarter of the microtubules displayed more expanded lattice spacings. The addition of the microtubule-stabilizing agent Taxol increased the lattice spacing of all microtubules, consistent with results on reconstituted microtubules. Furthermore, correlative cryo-light and electron microscopy revealed that the stable subset of microtubules labeled by StableMARK, a marker for stable microtubules, predominantly displayed a more expanded lattice spacing (∼41.9 Å), further suggesting a close connection between lattice expansion and microtubule stability. The coexistence of different lattices and their correlation with stability implicate lattice spacing as an important factor in establishing specific microtubule subsets.
微管在细胞中至关重要，其构象受到多种机制的调控，如翻译后修饰、微管相关蛋白和微管蛋白同工型。最近，微管晶格的构象也被认为是一个潜在的调节因子，但不同晶格在细胞内共存的程度仍不清楚。使用低温电子断层扫描技术，我们发现，虽然大多数微管具有致密的晶格（41 Å 单体间距），但大约四分之一的微管显示出更扩展的晶格间距。添加微管稳定剂紫杉醇会增加所有微管的晶格间距，这与重组微管的结果一致。此外，相关的低温光镜和电子显微镜显示，由 StableMARK 标记的稳定微管的稳定微管亚群主要显示出更扩展的晶格间距（41.9 Å），这进一步表明晶格扩展与微管稳定性之间存在密切联系。不同晶格的共存及其与稳定性的相关性表明晶格间距是建立特定微管亚群的重要因素。
