2025-10-02 スウェーデン王立工科大学(KTH)
<関連情報>
- https://www.kth.se/en/om/nyheter/centrala-nyheter/human-cilia-study-finds-new-proteins-offers-clues-to-childhood-disorders-1.1426690
- https://www.cell.com/cell/fulltext/S0092-8674(25)01029-3
空間プロテオミクスによって明らかになった一次繊毛の内在的異質性 Intrinsic heterogeneity of primary cilia revealed through spatial proteomics
Jan N. Hansen, ∙ Huangqingbo Sun, ∙ Konstantin Kahnert, ∙ … ∙ Anna Lindstrand, ∙ Ulrika Axelsson ∙ Emma Lundberg
Cell Published:September 25, 2025
DOI:https://doi.org/10.1016/j.cell.2025.08.039
Graphical abstract
Highlights
- Antibody-based spatial proteomics of primary cilia maps 715 ciliary proteins
- 3D confocal imaging resolves spatial microdomains in primary cilia
- 69% of ciliary proteins are cell-type specific, and 78% show single-cilium variation
- 91 novel ciliary proteins identified and CREB3 as a ciliopathy candidate gene
Summary
Primary cilia are critical organelles found on most human cells. Their dysfunction is linked to hereditary ciliopathies with a wide phenotypic spectrum. Despite their significance, the specific roles of cilia in different cell types remain poorly understood due to limitations in analyzing ciliary protein composition. We employed antibody-based spatial proteomics to expand the Human Protein Atlas to primary cilia. Our analysis identified the subciliary locations of 715 proteins across three cell lines, examining 128,156 individual cilia. We found that 69% of the ciliary proteome is cell-type specific, and 78% exhibited single-cilia heterogeneity. Our findings portray cilia as sensors tuning their proteome to effectively sense the environment and compute cellular responses. We reveal 91 cilia proteins and found a genetic candidate variant in CREB3 in one clinical case with features overlapping ciliopathy phenotypes. This open, spatial cilia atlas advances research on cilia and ciliopathies.
