HIF Stabilization Weakens Primary Cilia.
Although solitary or sensory cilia are present in most cells of the body and their existence has been known since the sixties, very little is known about their functions. One suspected function is fluid flow sensing- physical bending of cilia produces an influx of Ca++, which can then result in a variety of activated signaling pathways. Defective cilia and ciliary-associated proteins have been shown to result in cystic diseases. Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a progressive disease, typically appearing in the 5th decade of life and is one of the most common monogenetic inherited human diseases, affecting approximately 600,000 people in the United States. Because the mechanical properties of cilia impact their response to applied flow, we asked how the stiffness of cilia can be controlled pharmacologically. We performed an experiment subjecting cilia to Taxol (a microtubule stabilizer) and CoCl2 (a HIF stabilizer to model hypoxia). Madin-Darby Canine Kidney (MDCK) cells were selected as our model system. After incubation with a selected pharmacological agent, cilia were optically trapped and the bending modulus measured. We found that HIF stabilization significantly weakens cilia. These results illustrate a method to alter the mechanical properties of primary cilia and potentially alter the flow sensing properties of cilia.
Department of Physics, Cleveland State University, Cleveland, Ohio, United States of America.|Center for Gene Regulation in Health and Disease, Cleveland State University, Cleveland, Ohio, United States of America.
Andrew
A
Resnick
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D001696:Biomechanical Phenomena / Q000187:drug effects; D002923:Cilia / Q000187:drug effects* / Q000378:metabolism*; D003035:Cobalt / Q000494:pharmacology; D004285:Dogs; D061985:Madin Darby Canine Kidney Cells; D055595:Mechanical Phenomena / Q000187:drug effects*; D017239:Paclitaxel / Q000494:pharmacology; D055550:Protein Stability / Q000187:drug effects
D051792:Basic Helix-Loop-Helix Proteins; D003035:Cobalt; D017239:Paclitaxel; C018021:cobaltous chloride