TY - JOUR
T1 - The I1 dynein-associated tether and tether head complex is a conserved regulator of ciliary motility
AU - Fu, Gang
AU - Wang, Qian
AU - Phan, Nhan
AU - Urbanska, Paulina
AU - Joachimiak, Ewa
AU - Lin, Jianfeng
AU - Wloga, Dorota
AU - Nicastro, Daniela
N1 - Funding Information:
We thank Winfield S. Sale (Emory University) for generously providing antibodies against IC138, CK1, and PP2A (B sub). We also thank Xu Chen (Brandeis University) and Zhenguo Chen (UT Southwestern Medical Center) for management of the electron microscope facilities and training. The UT Southwestern Cryo-Electron Microscopy Facility is funded in part by CPRIT Core Facility Support Award RP170644. For LC-MS/MS analysis, we thank the proteomics core facilities at Harvard University and UT Southwestern Medical Center. We also thank Xiaowei Zhao (UT Southwestern Medical Center) for assisting with tomogram reconstruction. We are grateful to Jerry Brown and Long Gui for critical reading of the manuscript. This study was supported by the following grants: National Institutes of Health R01GM083122 to D.N., Polish Ministry of Science and Higher Education Grant No. N301706640 and National Science Centre, Poland, Grant 2014/14/M/NZ3/00511 (Harmonia 6) to D.W., and National Science Centre, Poland, Grant 2014/13/N/NZ3/04612 (Preludium 7) to P.U.
Publisher Copyright:
© 2018 Fu et al.
PY - 2018/5/1
Y1 - 2018/5/1
N2 - Motile cilia are essential for propelling cells and moving fluids across tissues. The activity of axonemal dynein motors must be precisely coordinated to generate ciliary motility, but their regulatory mechanisms are not well understood. The tether and tether head (T/TH) complex was hypothesized to provide mechanical feedback during ciliary beating because it links the motor domains of the regulatory I1 dynein to the ciliary doublet microtubule. Combining genetic and biochemical approaches with cryoelectron tomography, we identified FAP44 and FAP43 (plus the algae-specific, FAP43-redundant FAP244) as T/TH components. WT-mutant comparisons revealed that the heterodimeric T/TH complex is required for the positional stability of the I1 dynein motor domains, stable anchoring of CK1 kinase, and proper phosphorylation of the regulatory IC138-subunit. T/TH also interacts with inner dynein arm d and radial spoke 3, another important motility regulator. The T/TH complex is a conserved regulator of I1 dynein and plays an important role in the signaling pathway that is critical for normal ciliary motility.
AB - Motile cilia are essential for propelling cells and moving fluids across tissues. The activity of axonemal dynein motors must be precisely coordinated to generate ciliary motility, but their regulatory mechanisms are not well understood. The tether and tether head (T/TH) complex was hypothesized to provide mechanical feedback during ciliary beating because it links the motor domains of the regulatory I1 dynein to the ciliary doublet microtubule. Combining genetic and biochemical approaches with cryoelectron tomography, we identified FAP44 and FAP43 (plus the algae-specific, FAP43-redundant FAP244) as T/TH components. WT-mutant comparisons revealed that the heterodimeric T/TH complex is required for the positional stability of the I1 dynein motor domains, stable anchoring of CK1 kinase, and proper phosphorylation of the regulatory IC138-subunit. T/TH also interacts with inner dynein arm d and radial spoke 3, another important motility regulator. The T/TH complex is a conserved regulator of I1 dynein and plays an important role in the signaling pathway that is critical for normal ciliary motility.
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U2 - 10.1091/mbc.E18-02-0142
DO - 10.1091/mbc.E18-02-0142
M3 - Article
C2 - 29514928
AN - SCOPUS:85047368066
SN - 1059-1524
VL - 29
SP - 1048
EP - 1059
JO - Molecular biology of the cell
JF - Molecular biology of the cell
IS - 9
ER -