gli2 and gli3 localize to cilia and require the intraflagellar transport protein polaris for processing and functiongli2和激活本地化纤毛和需要intraflagellar运输蛋白质北极星为处理和功能.pdfVIP

Gli2 and Gli3 Localize to Cilia and Require the Intraflagellar Transport Protein Polaris for Processing and Function 1 1 2 1 2,3 1* Courtney J. Haycraft , Boglarka Banizs , Yesim Aydin-Son , Qihong Zhang , Edward J. Michaud , Bradley K. Yoder 1 Department of Cell Biology, University of Alabama, Birmingham, Alabama, United States of America, 2 University of Tennessee Oak Ridge National Laboratory Graduate School of Genome Science and Technology, University of Tennessee, Knoxville, Tennessee, United States of America, 3 Life Sciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee, United States of America Intraflagellar transport (IFT) proteins are essential for cilia assembly and have recently been associated with a number of developmental processes, such as left–right axis specification and limb and neural tube patterning. Genetic studies indicate that IFT proteins are required for Sonic hedgehog (Shh) signaling downstream of the Smoothened and Patched membrane proteins but upstream of the Glioma (Gli) transcription factors. However, the role that IFT proteins play in transduction of Shh signaling and the importance of cilia in this process remain unknown. Here we provide insights into the mechanism by which defects in an IFT protein, Tg737/Polaris, affect Shh signaling in the murine limb bud. Our data show that loss of Tg737 results in altered Gli3 processing that abrogates Gli3-mediated repression of Gli1 transcriptional activity. In contrast to the conclusions drawn from genetic analysis, the activity of Gli1 and truncated forms of Gli3 (Gli3R) are unaffected in Tg737 mutants at the molecular level, indicating that Tg737/Polaris is differentially involved in specific activities of the Gli proteins