Cilia protein map reveals causes of lung disease

Cilia are microscopic hair-like structures on cells that transport mucus and waste particles. They play roles in the airways, cerebrospinal fluid circulation, and reproduction. An inherited condition in which cilia move abnormally is called primary ciliary dyskinesia (PCD). It causes chronic lung infections, sinusitis, and in severe cases, fluid build-up in the brain (hydrocephalus).

The researchers mapped which proteins together form the so-called C2a projection, a component of cilia’s internal structure that controls how the hair-like structures move. They used three mouse models, each with one key gene knocked out. The results were published in eLife.

Every component is essential

The study shows that three proteins, CCDC108, MYCBPAP and CFAP70, maintain each other’s stability within the C2a structure. Remove any one of them, and the whole structure collapses. That leads to abnormal ciliary movement and all the associated disease symptoms. The researchers also identified two additional proteins in the structure: ARMC3 and MYCBP. These had not previously been linked to PCD.

Why does this matter for aging?

Cilia are not only relevant to inherited disease. With aging, ciliary function in the airways gradually declines, contributing to increased susceptibility to lung infections and to the slowing clearance of cerebrospinal fluid through the nasal cavity. The newly identified proteins are potential targets for understanding that age-related loss of ciliary function. This is still speculative: the study focuses on hereditary defects, not aging itself. But the molecular pathway described here is also active in older lungs.

The findings add to our understanding of how cilia are built at the molecular level and how protein loss leads to disease. Over time, that knowledge may prove relevant for developing treatments for both PCD and age-related lung problems.

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