ABSTRACT
Microtubules are vital components of the cytoskeleton. Their plus ends are dynamic and respond to changes in cell morphology, whereas the minus ends are stable and serve a crucial role in microtubule seeding and maintaining spatial organization. In mammalian cells, the calmodulin-regulated spectrin-associated proteins (CAMSAPs), play a key role in directly regulating the dynamics of non-centrosomal microtubules minus ends. However, the molecular mechanisms are not yet fully understood. Our study reveals that CAMSAP3 forms dimers through its C-terminal α-helix; this dimerization not only enhances the microtubule-binding affinity of the CKK domain but also enables the CKK domain to regulate the dynamics of microtubules. Furthermore, CAMSAP3 also specializes in decorating at the minus end of microtubules through the combined action of the microtubule-binding domain (MBD) and the C-terminal α-helix, thereby achieving dynamic regulation of the minus ends of microtubules. These findings are crucial for advancing our understanding and treatment of diseases associated with non-centrosomal microtubules.
Footnotes
Author contributions
Conceptualization: Y.L., R.Z., X.L., W.M.; Data curation: Y.L., R.Z., J.R.; Investigation: Y.L., R.Z.; Methodology: Y.L., R.Z., J.R., W.C., Z.Z., H.X., D.L., H.C., Q.X., W.J., W.F., X.L., W.M.; Supervision: X.L., W.M.; Visualization: Y.L., R.Z., J.R.; Writing – original draft: Y.L., R.Z., W.M.; Writing – review & editing: Y.L., R.Z., X.L., W.M.
Funding
This work was funded by the National Natural Science Foundation of China (31930025, 32070704 and 32100760) and the National Key Research and Development Program of China (2021YFA0804802).
Data availability
All relevant data can be found within the article and its supplementary information.
