Nearly all human cells have cilia, but these structures have been largely ignored by biologists, researchers, and clinicians. That’s changing.
What were once thought of as nonfunctional vestigial relics of evolutionary history are emerging as critical components in multiple signaling pathways that control sight, smell, renal function, feeding behavior and obesity, skeletal formation, and, most recently, insulin secretion and glucose homeostasis.
“Cell-surface receptors on cilia can be remarkably sensitive, responding to single photons in retinal cells and single molecules in olfactory cells in the nose,” said Peter K. Jackson, PhD, Stanford University School of Medicine. “Retinal degeneration, loss of smell, obesity from loss of feeding control, and reduced insulin secretion in response to glucose can all result from dysfunctional ciliary signaling. The cilia are like tape players, and when they malfunction, the song is distorted and function suffers.”
Dr. Jackson will provide an overview of ciliary function and describe their activity to regulate pancreatic islet hormone secretion during the symposium How Cilia Direct Pancreatic Islet Function. The two-hour session begins at 7:30 a.m. CT Tuesday, June 7, in Room 208 at the convention center.
Pancreatic islets are active in multiple regulatory pathways involving different G-protein-coupled receptors, Dr. Jackson explained. Cilia on alpha, beta, and delta cells are actively involved in glucose homeostasis by way of response to glucose, glucagon-like peptide-1 (GLP-1), omega-3 fatty acids, prostaglandins, and other hormones and metabolites.
“It has been known through dietary studies that supplementation with omega-3 fatty acids can improve insulin secretion,” Dr. Jackson said. “We now have a mechanistic pathway in pancreatic islet beta cells that uses a specific receptor in specific contexts that cooperate nicely with GLP-1 and other drugs to improve glucose-dependent insulin responses. This offers a new vision of signaling, new targets, and a new body of exploration that can give us a better sense of how insulin secretion could be controlled with new biomarkers and new therapeutics.”
Cilia haven’t just been ignored for decades, they have been misunderstood and misclassified. Most current biology texts classify cilia as primary, or strictly sensory, versus motile. Recent improvements in imaging technology have revealed that primary cilia are in near-constant motion.
“When we made a cilia reporter—a fluorescent label for cilia to study them in real time in live islet cells—the first thing we noticed was that the cilia move,” said Jing Hughes, MD, PhD, Washington University School of Medicine. “This is new biology and new functionality.”
Dr. Hughes likens cilia to cellular antennas that can sense molecules and respond to molecular signals. The ability of each cilium to move nearly 360 degrees and to physically touch its neighbors increases sensitivity and allows for direct cell-to-cell signaling.
“If you think about islet function, it’s all about how well cells are synchronized,” she said. “Beta cells have to be synchronized to put out a massive amount of insulin whenever there’s a big glucose load, and to turn off just as quickly. Alpha cells, secreting glucagon, and delta cells, secreting somatostatin, have to respond just as quickly. Motile cilia allow cells to function more efficiently by talking directly to their neighbors and to respond to circulating glucose and other molecules. Cilia biology is going to explode in diabetes. This nanomachine on the cell surface, which is ignored in all the textbooks, coordinates so much of beta-cell function and dysfunction. There is enormous potential for clinical translation.”