Our Cells' Cilia May Be Linked to Many Diseases

In the August 4 issue of the journal Science, Jeremy Reiter, MD, PhD, a UCSF fellow in biochemistry and human genetics, co-writes an article laying out an emerging view that cilia - those tiny projections in nearly every human cell, from kidney to skin and brain and pancreas - may be key players in signaling within cells and, when defective, may underlie many serious diseases. Reiter, who will become assistant professor of biochemistry and human genetics at UCSF in September, is a researcher in both the UCSF Diabetes Center and the Institute for Regeneration Medicine. He wrote the article in Science with biochemistry graduate student Veena Singla. We asked Reiter how this unusual research emerged, and where it may be going. Q. Research in your lab and in others is starting to reveal that cilia - present in almost all vertebrate cells - are not just critical for sensation and movement within cells, but also key participants in signaling within cells. What is the evidence? A. Probably the most famous example is found in the retina. The cells at the back of our eye that sense light are called rod cells and cone cells. The rods and cones of their names refer to a modified cilium that can look a bit like a rod or a cone under a microscope. Within these modified cilia are the proteins that detect light (the opsins). Not only that, but the molecular machinery that translates that initial event into chemical messengers also acts at these cilia. As people have examined the role of cilia outside of the eye, they have found that they can act in many other signaling events. For example, the initial events of smell take place on cilia in the nose. Cilia also seem to detect urine production in the kidney. And more recent work suggests that cilia can detect signals sent from one cell to another that are used to control basic behaviors, such as whether to divide or what type of cell to become. Q. Why do you think this emerging understanding is important? A. Defects in the signaling functions of cilia cause important human diseases. Probably the most important is polycystic kidney disease (PKD). In PKD, defects in the ability of cilia to detect urine production result in increased cell proliferation. Those proliferating cells form cysts that crowd out the normal cells, leading to kidney failure. About half a million Americans have PKD, and there is no cure. Ciliary defects may underlie other diseases, as well - retinal degeneration, infertility and birth defects, such as some forms of heart defects and spina bifida.

Primary cilia (blue) emerging from the cells of a mouse embryo (green).

Q. How did you come to be interested in cilia as a research subject? A. I wish I could say that some profound insight led me to be interested in this poorly understood appendage to the cell. However, like a lot of researchers, my path was pretty circuitous. I'm mostly interested in how cells talk to each other, and how this goes awry in disease. This led to an interest in how cells interpret the signals that they send to each other, and that led to cilia - a kind of antenna that the cell uses to detect a diverse array of different kinds of information in its environment. Q. What do you find most interesting about this research? A. I guess what I like most is how this research highlights how much remains to be discovered in biology. Certainly, I didn't learn anything about the signaling functions of cilia in my college biology courses. It seems like if you start out from established biological fact and take three steps in any direction, you arrive at a new, entirely uncharted and very interesting place. Q. Where do you hope this research will lead? A. It's still in the early days of this research, but I hope that understanding how cilia function will provide new treatments for diseases caused by malfunctioning cilia, such as polycystic kidney disease. One of the benefits about basic science research is that this could also develop in unanticipated ways that might provide unexpected benefits. For example, we're currently exploring whether cilia have a role in cancer.

"The Primary Cilium as the Cell's Antenna: Signaling at a Sensory Organelle" Veena Singla and Jeremy F. Reiter Science 2006 313(5787):629-633 Abstract | Full Text | Full Text (PDF)