Protein critical to cilia development

NIH | JULY 20, 2014

Some single-celled creatures have structures called motile cilia that beat rhythmically to allow the cells to move. Motile cilia are also found in larger organisms, including people. For example, motile cilia are on cells that line the trachea, where their coordinated wave-like motions carry mucus—along with the inhaled dust, bacteria, and other small particles it contains—toward the mouth to be coughed or sneezed out of the body.

Cilia that aren’t involved in movement are called primary cilia. These cilia are responsible for cell communication. They also play a key role in the receptor cells of sensory systems. For example, they’re essential for odor detection in the nose and light reception in the eye.

Defects in genes that are involved in cilia development or function can cause complicated syndromes, called ciliopathies, that involve multiple organs and tissues. Bardet-Biedl and Joubert syndromes are ciliopathies with many symptoms that may include deafness, kidney disease, and retina degeneration. Meckel syndrome is a ciliopathy so dangerous that babies with the genetic defect rarely make it to term.

Researchers have identified several genes that are essential to form and maintain cilia. One important gene involved in ciliopathies is CC2D2A. The CC2D2A protein was thought to be a structural protein needed for cilia growth, but its precise functions have been unclear. The protein is part of a complex structure called the basal body, from which cilia grow.

To investigate CC2D2A function, a team led by Drs. Shobi Veleri and Anand Swaroop at NIH’s National Eye Institute (NEI) developed mice lacking the mouse version of the gene, Cc2d2a.

The researchers found that mice without Cc2d2a were unable to develop past the early embryo stage. An examination of tissues in early development revealed few to no cilia. The findings suggest that Cc2d2a plays a critical role early in development. Looking closely at where the cilia should exist, the researchers saw that the supporting structures needed for cilia to grow were either completely missing or abnormal.

The absence of Cc2d2a affected genes and proteins involved in the development of many mouse tissues, including sonic hedgehog, a key signaling protein. Other experiments showed that CC2D2A is part of structures called subdistal appendages, which help anchor the basal body at the cell membrane to stabilize cilia and allow them to form.

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