EFCAB10 anchors AK8 to the radial spoke for proper ciliary motility
Abstract
Radial spokes in motile cilia and flagella regulate rhythmic ciliary motility, which is essential for rapid cell movement and extracellular fluid flow. In humans, defective radial spokes can cause a genetic disorder known as primary ciliary dyskinesia (PCD), resulting in respiratory defects and infertility. Despite their critical role in ciliary motility, the molecular composition and related physiological functions remain to be elucidated. Here, we identify EF-hand calcium-binding domain protein 10 (EFCAB10) and adenylate kinase (AK8) as radial spoke proteins and describe their roles in mouse motile cilia. Using Efcab10 −/− and Ak8 −/− mice, we show that loss of either protein can affect ciliary motility and lead to PCD-related phenotypes in mice. Interestingly, ciliary AK8 is completely absent in Efcab10 −/− cilia, but the loss of AK8 has no effect on ciliary EFCAB10. Further biochemical analyses reveal that EFCAB10 interacts with AK8 and RSPH3B, which fastens AK8 to the radial spoke. Overall, our findings demonstrate the essential role of EFCAB10 as a radial spoke protein in maintaining the integrity of the radial spoke and provide valuable insights into the molecular basis of related ciliopathies.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (14)
Ting Song
Center for Cell Structure and Function, Shandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Shandong Normal University
Qingchao Li
Center for Cell Structure and Function, Shandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Shandong Normal University
Qian Lyu
Center for Cell Structure and Function, Shandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Shandong Normal University
Junkui Zhao
State Key Laboratory of Medicinal Chemical Biology, Haihe Laboratory of Cell Ecosystem, College of Life Sciences, Nankai University
Xirui Zi
Center for Cell Structure and Function, Shandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Shandong Normal University
Shuxiang Ma
Center for Cell Structure and Function, Shandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Shandong Normal University
Jiajun Luo
Key Laboratory of Multi-Cell Systems, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, University of Chinese Academy of Sciences, Chinese Academy of Sciences
Shushen Li
Center for Cell Structure and Function, Shandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Shandong Normal University
Shanshan Nai
Center for Cell Structure and Function, Shandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Shandong Normal University
Hongbin Liu
Cheeloo College of Medicine, Shandong University
Xueliang Zhu
Key Laboratory of Multi-Cell Systems, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, University of Chinese Academy of Sciences, Chinese Academy of Sciences
Te Li
State Key Laboratory of Medicinal Chemical Biology, Haihe Laboratory of Cell Ecosystem, College of Life Sciences, Nankai University
Jun Zhou
Huijie Zhao
Center for Cell Structure and Function, Shandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Shandong Normal University