biostudies-literatureLi MMOST | National Key Research and Development Program of China (NKPs)MOST | National Natural Science Foundation of China (NSFC)MOST | National Key Research and Development Program of ChinaMOST | National Natural Science Foundation of Chinae2414731122https://www.ebi.ac.uk/biostudies/studies/S-EPMC12012489biostudies-literatureUnknown122(15)The tubulin tail is a key element for microtubule (MT) functionality, but the functional redundancy of tubulin genes complicates the genetic determination of their physiological functions. Here, we removed the C-terminal tail of five alpha- and four beta-tubulin genes in the <i>C. elegans</i> genome. Sensory cilia typically exhibit an axoneme that longitudinally differentiates into a middle segment with doublet MTs and a distal segment with singlet MTs. However, the excision of the alpha-tubulin tail, but not the beta-tubulin tail, resulted in the ectopic formation of doublet MTs in the distal segments. Molecular dynamics simulations suggest that the alpha-tubulin tail could prevent the B-tubule from docking on the surface of A-tubule. Using recombinant tubulins, we demonstrated that removProceedings of the National Academy of Sciences of the United States of AmericaAlpha-tubulin tails regulate axoneme differentiation.PMC12012489922543062022YFA130270032270773322707213207070632470730319911902019YFA0508401Li WGuo ZChen ZOu GWang YChai YLi MfalseAlpha-tubulin tails regulate axoneme differentiation.The tubulin tail is a key element for microtubule (MT) functionality, but the functional redundancy of tubulin genes complicates the genetic determination of their physiological functions. Here, we removed the C-terminal tail of five alpha- and four beta-tubulin genes in the <i>C. elegans</i> genome. Sensory cilia typically exhibit an axoneme that longitudinally differentiates into a middle segment with doublet MTs and a distal segment with singlet MTs. However, the excision of the alpha-tubulin tail, but not the beta-tubulin tail, resulted in the ectopic formation of doublet MTs in the distal segments. Molecular dynamics simulations suggest that the alpha-tubulin tail could prevent the B-tubule from docking on the surface of A-tubule. Using recombinant tubulins, we demonstrated that remov2025-01-01T00:00:00Z2025 Apr2026-07-15T07:34:00.634Z2026-07-02T03:08:40.785ZS-EPMC120124894019870310.1073/pnas.2414731122