In situ structure of the human ciliary transition zone links linker defects to primary ciliary dyskinesia.

Authors

Haixia Zhou, Lea Terbeck, Andrew Berical, Marine Brunet, Sven M Lange, Jacob R Anderson, Heike Olbrich, Diana Carolin Bracht, Kai Wohlgemuth, Cynthia Rieck, Johanna Raidt, Jürgen Klingauf, Sivagurunathan Sutharsan, Huda Mussaffi, Dario Prais, Victoria Dunphy, Sachiko T Homma, Paul Guichard, Virginie Hamel, Finn J Hawkins, Heymut Omran, Alan Brown

Published in

Science (New York, N.Y.). Pages eaei5957. Sep 10, 2026. Epub Sep 10, 2026.

Abstract

The ciliary transition zone (TZ) regulates ciliary proteome composition, yet its molecular architecture, protein content, and contribution to motile ciliopathies remain poorly defined. We applied in situ cryo-electron tomography and subtomogram averaging to human multiciliated epithelial cells. This approach resolved TZ-specific doublet microtubules at subnanometer resolution and identified nine constituent proteins. We identified that ECT2L and DZANK1 form the major linker complexes between adjacent TZ doublet microtubules. Biallelic loss-of-function variants in either gene cause primary ciliary dyskinesia. ECT2L and DZANK1 deficiency disrupted TZ architecture, caused microtubular abnormalities and abnormal bulbous ciliary tips, and impaired mucociliary clearance. These findings establish a direct genetic link between TZ defects and human motile ciliopathy, and illustrate how in situ structural biology can uncover mechanisms of human disease.

PMID:
42721274
Bibliographic data and abstract were imported from PubMed on 11 Sep 2026.

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