Journal
MOLECULAR BIOLOGY OF THE CELL
Volume 29, Issue 9, Pages 1048-1059Publisher
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E18-02-0142
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Funding
- CPRIT [RP170644]
- National Institutes of Health [R01GM083122]
- Polish Ministry of Science and Higher Education [N301706640]
- National Science Centre, Poland [2014/14/M/NZ3/00511, 2014/13/N/NZ3/04612]
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM083122] Funding Source: NIH RePORTER
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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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