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

In situ cryo-electron tomography reveals that ECT2L and DZANK1 form major linker complexes in the human ciliary transition zone, and their loss causes primary ciliary dyskinesia.

• Why it matters: Understanding the molecular architecture of the ciliary transition zone is crucial because its defects are linked to motile ciliopathies like primary ciliary dyskinesia, but its detailed structure and protein content remain poorly defined.
• What they did: The study used in situ cryo-electron tomography and subtomogram averaging on human multiciliated epithelial cells to resolve TZ-specific microtubules at subnanometer resolution and identify nine constituent proteins, focusing on ECT2L and DZANK1.
• The result: Loss-of-function variants in ECT2L or DZANK1 disrupt TZ architecture, cause microtubular abnormalities and bulbous ciliary tips, impair mucociliary clearance, and establish a direct genetic link between TZ defects and human motile ciliopathy.