Movie
Controller
Structure viewers
About Yorodumi Papers
+Search query
-Structure paper
| Title | The luminal ring protein C2CD3 acts as a radial in-to-out organizer of the distal centriole and appendages. |
|---|---|
| Journal, issue, pages | PLoS Biol, Vol. 23, Issue 12, Page e3003519, Year 2025 |
| Publish date | Dec 9, 2025 |
 Authors | Eloïse Bertiaux / Vincent Louvel / Caitlyn L McCafferty / Hugo van den Hoek / Umut Batman / Souradip Mukherjee / Lorène Bournonville / Olivier Mercey / Isabelle Méan / Ricardo D Righetto / Adrian Müller / Philippe Van der Stappen / Garrison Buss / Jean Daraspe / Christel Genoud / Tim Stearns / Benjamin D Engel / Virginie Hamel / Paul Guichard /   |
| PubMed Abstract | Centrioles are polarized microtubule-based structures with appendages at their distal end that are essential for cilia formation and function. The protein C2CD3 is critical for distal appendage ...Centrioles are polarized microtubule-based structures with appendages at their distal end that are essential for cilia formation and function. The protein C2CD3 is critical for distal appendage assembly, with mutations linked to orofaciodigital syndrome and other ciliopathies. However, its precise molecular role in appendage recruitment remains unclear. Using ultrastructure expansion microscopy (U-ExM) and iterative U-ExM on human cells, together with in situ cryo-electron tomography (cryo-ET) on mouse tissues, we reveal that C2CD3 adopts a radially symmetric 9-fold organization within the centriole's distal lumen. We show that the C-terminal region of C2CD3 localizes close to a ~100 nm luminal ring structure consisting of ~27 nodes, while its N-terminal region localizes close to a hook-like structure that attaches to the A-microtubule as it extends from the centriole interior to exterior. This hook structure is adjacent to the DISCO complex (MNR/CEP90/OFD1), which marks future appendage sites. C2CD3 depletion disrupts not only the recruitment of the DISCO complex via direct interaction with MNR but also destabilizes the luminal ring network composed of C2CD3/SFI1/centrin-2/CEP135/NA14, as well as the distal microtubule tip protein CEP162. This reveals an intricate "in-to-out" molecular hub connecting the centriolar lumen, distal microtubule cap, and appendages. Although C2CD3 loss results in shorter centrioles and appendage defects, key structural elements remain intact, permitting continued centriole duplication. We propose that C2CD3 forms the luminal ring structure and extends radially to the space between triplet microtubules, functioning as an architectural hub that scaffolds the distal end of the centriole, orchestrating its assembly and directing appendage formation. |
 External links | PLoS Biol / PubMed:41364719 / PubMed Central |
| Methods | EM (tomography) / EM (subtomogram averaging) |
| Resolution | 36.0 - 38.0 Å |
| Structure data |  EMDB-55386: Tomogram of a mouse tracheal epithelial cell containing the C2CD3 luminal ring protein  EMDB-55390: In situ cryo-electron tomogram of a mouse rod photoreceptor cell containing the centriolar luminal distal ring  EMDB-55391: In situ cryo-electron tomogram of a mouse rod photoreceptor cell containing the centriolar luminal distal ring  EMDB-55393: Subtomogram average of the hook density between microtubule doublets/triplets  EMDB-55394: Subtomogram average of the luminal distal ring from MTEC centrioles |
| Source |
|
Mus musculus (house mouse)