’Cellular antennae’ on algae give clues to how human cells receive signals

Cilia perform many functions on human cells; they propel egg and sperm cells to make fertilization possible, line the nose to pick up odors, and purify the blood, among other tasks.

With such a range of abilities, cilia serve as both motors and “cellular antennae,” said Dr. William Snell, a professor of cell biology at UT Southwestern and senior author of new research on cilia published in the May 5 issue of Cell.

Genetic defects in cilia can cause people to develop debilitating kidney disease or to be born with learning disabilities, extra fingers or toes, or the inability to smell.

But no one really knows how cilia work, or, in some parts of the body, what their function is.

“There are cilia all over within our brain, and we don’t have a clue about what they’re doing,” Dr. Snell said.

He and his team use the microscopic green alga, Chlamydomonas reinhardtii, which has two individual cilia. This alga allows researchers to manipulate genes and study the resulting effects on cilia in a way that would be impossible in animals such as mice.

“Chlamy is one of the few model organisms in which it’s possible to do these kinds of studies,” Dr. Snell said. Normally, cilia — also called flagella — are built and maintained by an internal bidirectional, escalator-like system that ferries molecules to and from the tips by a process called intraflagellar transport, or IFT.

The UT Southwestern researchers used a mutant temperature-sensitive strain of the alga that behaved normally at lower temperatures. At higher temperatures, however, the IFT process stopped, and its components disappeared from the cilia. The cilia themselves were still able to beat, or move back and forth, for about 40 minutes before they began to shorten.

The team focused on fertilization of the alga, a process that requires a cilium to bind to a molecule on a cilium from a cell of the opposite mating type. They found that when the external molecule binds to a cilium, it activates an enzyme that signals the start of a chain of chemical reactions.

Although the cilia could move without IFT and bind to the molecules of the cilia of the opposite type, those cells were unable to respond to the signaling molecules. The failure to activate the chain of chemical reactions indicated that IFT was necessary for this function.

Analysis showed that the cilia signaling process was similar to that found in human cells, such as those in the nose involved in the sense of smell and those in the developing nervous system that sculpt our brains.

Uncovering this series of reactions will make it possible to test, for instance, drugs that can affect cilia, in the hope of finding substances that would also be effective in higher animals, Dr. Snell said.

“This is another example of how basic science research can have big results,” he said. “Studies on Chlamydomonas will help us understand the unique qualities of cilia that have led to their use in chemosensory pathways in humans.”

Other UT Southwestern researchers involved in the study were Dr. Qian Wang, lead author and postdoctoral researcher in cell biology, and Dr. Junmin Pan, assistant professor of cell biology.

The work was supported by the National Institutes of Health.