Structure of the mammalian ciliary transition zone microtubule doublet

Cai, B.; Camardiel, A.; Grinsven, E.; Veghel, T.; Aher, A.; Aarts, E.; Xu, Y.; Beltrao, P.; Beekman, J.; Akhmanova, A.; Xu, J.; Wieczorek, M.

doi:10.64898/2026.06.11.731632

bioRxiv · 10.64898/2026.06.11.731632

Structure of the mammalian ciliary transition zone microtubule doublet

Cai, B.·Camardiel, A.·Grinsven, E.·Veghel, T.·Aher, A.·Aarts, E.·Xu, Y.·Beltrao, P.·Beekman, J.·Akhmanova, A.·Xu, J.·Wieczorek, M.

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Abstract

The ciliary transition zone gates bidirectional protein trafficking to maintain the specialized ciliary proteome using microtubule doublets as a scaffold. While ciliary axonemal doublets are well-characterized, the molecular architecture of the transition zone doublet remains elusive. Here, we report the structure of the mammalian transition zone doublet from bovine tracheal cilia using cryo-electron tomography at 4.7-5.0 [A] resolution. The transition zone doublet is a structurally independent segment defined by an 8 nm-periodic arrangement of unique microtubule-inner proteins (MIPs) and microtubule-associated proteins (MAPs). We identify the calcium-binding protein CAPSL as a lumenal MIP that forms a pseudo-helical spiral and stabilizes microtubules in vitro. Furthermore, a dense MAP network on the A-microtubule surface clashes with intraflagellar transport (IFT) motor binding sites, suggesting anterograde IFT is directed to the B-microtubule for potential regulation by MAP9. Our work provides a structural framework for understanding gated ciliary transport and transition zone-linked human ciliopathies.

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Cai, B., Camardiel, A., Grinsven, E., Veghel, T., Aher, A., Aarts, E., Xu, Y., Beltrao, P., Beekman, J., Akhmanova, A., Xu, J., Wieczorek, M.. 2026-06-12. Structure of the mammalian ciliary transition zone microtubule doublet. https://doi.org/10.64898/2026.06.11.731632

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