“Champagne corks” at microtubule tips control growth of cilia

A network of interacting ciliary tip proteins with opposing activities imparts slow and processive microtubule growth.

Saunders HAJ, van den Berg CM, Hoogebeen RA, Schweizer D, Stecker KE, Roepman R, Howes SC, Akhmanova A.
Nat Struct Mol Biol. 2025 Jan 24. doi: 10.1038/s41594-025-01483-y.
PMID: 39856351

Cilia are small, hair-like structures found on many eukaryotic cells that help with movement or sensing the environment. Their formation and function depend on microtubules, which grow very slowly, though the reasons for this have been unclear. In this study, the Akhmanova lab in collaboration with the labs of Stuart Howes and Kelly Stecker at the Bijvoet Center for Biomolecular Research at Utrecht University and Ronald Roepman at the Radboud UMC in Nijmegen recreated the behavior of five proteins—CEP104, CSPP1, TOGARAM1, ARMC9, and CCDC66—that work together at the tips of cilia. These proteins interact with microtubules and with each other, and mutations in them can cause diseases like Joubert syndrome. Researchers found that CEP104 and CSPP1 slow down microtubule growth, while TOGARAM1 can reverse this effect. ARMC9 and CCDC66 don’t directly affect microtubules but help organize the other proteins. Using cryo-electron tomography, they showed that these proteins form a cork-like structure at microtubule ends, which stabilizes microtubules and allows for the very slow, steady growth needed for proper cilia function. These findings have implications for understanding human ciliopathies and development of new treatments of these disorders.