Scientists identify critical protein complex in formation of cell cilia

Aug 19, 2008

An international team led by NYU Cancer Institute have identified a protein complex that regulates the formation of cilia, which are found on virtually all mature human cells and are essential to normal cell function.

The new report, published this week by Developmental Cell and selected as the featured publication of the open-access online edition, describes how three proteins work together to regulate the formation of primary cilia. The study led by Brian Dynlacht, Ph.D., professor of pathology and director of NYU Cancer Institute Genomics Facility, investigates these antenna-like structures, once thought to be vestigial remnants of cell evolution, which have recently emerged as a focal point of research in developmental cell biology.

"We are trying to understand the regulation of processes that are fundamental to normal cell development and health in humans," said William Y. Tsang, Ph.D., of the NYU School of Medicine and Cancer Institute, and first author of the paper. "Defective cilia are implicated in a wide range of serious illnesses such as polycystic kidney disease, retinal degeneration, and neurological disorders. Inappropriate activation of signaling molecules that normally reside at the primary cilium, may lead to certain cancers."

At the center of the process lies the protein CEP290, which normally promotes primary cilia formation in mature cells. Dr. Tsang and his colleagues discovered that a second protein, CP110, normally suppresses the function of CEP290 until cells are fully mature. At that point, CP110 is destroyed, freeing CEP290 to interact with a third protein, Rab8a, to promote cilia formation on the surface of the mature cell.

The team's findings may help to identify potential targets for future drug design.

"Ciliogenesis is a fundamental process. These structures are found in almost every type of human cell you can imagine," Dr. Tsang said. "If we can ever design drugs that will restore the formation and function of cilia even in the presence of CEP290 mutations, then that would be one way to cure the defects that lead to ciliary diseases."

Research so far has been using in vitro human cell lines. However, team members from the University of Michigan and National Eye Institute have developed a mouse model with a CEP290 mutation implicated in retinal degeneration, and the NYU group is planning a study of human CEP290 mutations to see if they can correlate genotypes to their expression in specific ciliary diseases.

Source: NYU Langone Medical Center / New York University School of Medicine

Explore further: Shark's unique trek could help save the species

Related Stories

Researchers image and measure tubulin transport in cilia

Jan 26, 2015

Defective cilia can lead to a host of diseases and conditions in the human body—from rare, inherited bone malformations to blindness, male infertility, kidney disease and obesity. Scientists knew that somehow ...

Recommended for you

Shark's unique trek could help save the species

6 hours ago

Her name is Jiffy Lube2, a relatively small shortfin mako shark that, like others of her kind, swims long distances every day in search of prey and comfortable water temperatures.

Researchers discover new mechanism of DNA repair

Jul 03, 2015

The DNA molecule is chemically unstable giving rise to DNA lesions of different nature. That is why DNA damage detection, signaling and repair, collectively known as the DNA damage response, are needed.

The math of shark skin

Jul 03, 2015

"Sharks are almost perfectly evolved animals. We can learn a lot from studying them," says Emory mathematician Alessandro Veneziani.

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.