biostudies-literatureCeglowski JHHS | NIH | NIDDK | Division of Diabetes, Endocrinology, and Metabolic DiseasesHHS | NIH | National Institute of General Medical SciencesNIDDK NIH HHSBolie Scolar AwardNIGMS NIH HHS198-227https://www.ebi.ac.uk/biostudies/studies/S-EPMC10883266biostudies-literatureUnknown25(1)The primary cilium is a critical sensory organelle that is built of axonemal microtubules ensheathed by a ciliary membrane. In polarized epithelial cells, primary cilia reside on the apical surface and must extend these microtubules directly into the extracellular space and remain a stable structure. However, the factors regulating cross-talk between ciliation and cell polarization, as well as axonemal microtubule growth and stabilization in polarized epithelia, are not fully understood. In this study, we find TTLL12, a previously uncharacterized member of the Tubulin Tyrosine Ligase-Like (TTLL) family, localizes to the base of primary cilia and is required for cilia formation in polarized renal epithelial cells. We also show that TTLL12 directly binds to the α/β-tubulin heterodimer in vitEMBO reportsTTLL12 is required for primary ciliary axoneme formation in polarized epithelial cells.PMC10883266T32-GM136444R01 DK064380DK064380T32 GM136444R35 GM136253Neumann AJHoffman HKCeglowski JMcCurdy BLMoore JKHoff KJPrekeris RfalseTTLL12 is required for primary ciliary axoneme formation in polarized epithelial cells.The primary cilium is a critical sensory organelle that is built of axonemal microtubules ensheathed by a ciliary membrane. In polarized epithelial cells, primary cilia reside on the apical surface and must extend these microtubules directly into the extracellular space and remain a stable structure. However, the factors regulating cross-talk between ciliation and cell polarization, as well as axonemal microtubule growth and stabilization in polarized epithelia, are not fully understood. In this study, we find TTLL12, a previously uncharacterized member of the Tubulin Tyrosine Ligase-Like (TTLL) family, localizes to the base of primary cilia and is required for cilia formation in polarized renal epithelial cells. We also show that TTLL12 directly binds to the α/β-tubulin heterodimer in vit2024-01-01T00:00:00Z2024 Jan2026-07-14T18:23:55.52Z2025-02-19T03:51:14.807ZS-EPMC108832663817790810.1038/s44319-023-00005-5