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Mol Biol Cell. 2018 May 1;29(9):1048-1059. doi: 10.1091/mbc.E18-02-0142. Epub 2018 Mar 22.

The I1 dynein-associated tether and tether head complex is a conserved regulator of ciliary motility.

Author information

1
Departments of Cell Biology and Biophysics, University of Texas Southwestern Medical Center, Dallas, TX 75235.
2
Laboratory of Cytoskeleton and Cilia Biology, Department of Cell Biology, Nencki Institute of Experimental Biology of Polish Academy of Sciences, 02-093 Warsaw, Poland.

Abstract

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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