Seeking the Causes of Ciliary Dyskinesia

diagrams of genes in Chlamydomonas and humans

Cilia and flagella are small, hairlike protrusions that are found on the surface of a cell body. They can be sense organs, or they can move, beating in a coordinated motion to either move the cell or to move liquids or small solids across the cell surface. A disease known as primary ciliary dyskinesia (PCD) can cause a number of human disorders. One of these is chronic destructive airway disease, where the cilia of the respiratory system are unable to move mucus out of the airways, and male infertility caused by poor movement of sperm flagella.

Professor Mary Porter (Genetics, Cell Biology, and Development) and her research group and collaborators are studying the proteins that regulate the activity of dynein motors in cilia and flagella. They are using software available through MSI to analyze and compare wild-type and mutant strains in the Chlamydomonas, a type of algae that moves using flagella. Results from studying Chlamydomonas can be applied to research in humans.

In research published last year in the journal Nature Genetics, Professor Porter and her colleagues discovered genetic mutations that are involved in PCD pathogenesis (“The nexin-dynein regulatory complex subunit DRC1 is essential for motile cilia function in algae and humans,” M. Wirschell, H. Obrich, C. Werner, D. Trischler, R. Bower, W.S. Hale, N.T. Loges, P. Pennekamp, S. Lindberg, U. Stenram, B. Carlen, E. Horak, G. Kohler, P. Nurnberg, G. Nurnberg, M.E. Porter, and H. Omran, Nature Genetics 45, 262-268 (2013)). They have identified the DRC1 subunit of the nexin-dynein regulatory complex, and showed that mutations disrupting DRC1 result in defects that can cause cilia to be defective. This is the first direct evidence that mutations in DRC genes cause human disease.

Image description: Diagrams of the DRC1 subunit in Chlamydomonas (top) and its human counterpart CCDC164 (bottom). The coiled-coil motifs are shown in dark gray. The positions of the protein alterations identified in algae and human are indicated with arrows. (Image and description from M. Wirschell et al., Nature Genetics 45, 262-268 (2013). © Nature Genetics)

posted on March 5, 2014

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