Simulation of intra-ciliary diffusion suggests a novel role of primary cilia as a cell-signaling enhancer

Besides the role to generate a fluid flow in the surrounding medium, eukaryotic cilia have a crucial function in sensing external signals such as chemical or mechanical stimuli. A large body of work has shown that cilia are frequently found in various types of sensory cells and are closely related to many regulatory mechanisms in differentiation and development. However, we do not yet have a definitive answer to the fundamental question, "why cilia?" It has been a long-standing mystery why cells use cilia for sensing external signals. To shed light on this, we sought to describe the kinetics of signaling with theoretical approaches. Based on the results, here we propose a new role of cilia as a cell-signaling enhancer. The enhancing effect comes from restricted volume for the free intra-ciliary diffusion of molecules due to the cylindrical shape of cilia, which can facilitate quick accumulation of intracellular signaling molecules. Our simulations demonstrate that both the rate and amplitude of response in signal transduction depend on where the membrane receptors or channels are located along the ciliary shaft. In addition, the calculated transfer function of cilia regarded as a transmitter of external signals also suggests the properties of cilia as a signal enhancer. Since such unique composition of receptors and channels in cilia is found in various types of eukaryotic cells, signal enhancing is presumably one of the most essential and conserved roles of cilia.