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

Gang Fu, Qian Wang, Nhan Phan, Paulina Urbanska, Ewa Joachimiak, Jianfeng Lin, Dorota Wloga, Daniela Nicastro

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1048-1059
Number of pages12
JournalMolecular Biology of the Cell
Volume29
Issue number9
DOIs
StatePublished - May 1 2018

Fingerprint

Dyneins
Head
Axonemal Dyneins
Critical Pathways
Cilia
Microtubules
Molecular Biology
Arm
Phosphotransferases
Tomography
Phosphorylation

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

The I1 dynein-associated tether and tether head complex is a conserved regulator of ciliary motility. / Fu, Gang; Wang, Qian; Phan, Nhan; Urbanska, Paulina; Joachimiak, Ewa; Lin, Jianfeng; Wloga, Dorota; Nicastro, Daniela.

In: Molecular Biology of the Cell, Vol. 29, No. 9, 01.05.2018, p. 1048-1059.

Research output: Contribution to journalArticle

Fu, Gang ; Wang, Qian ; Phan, Nhan ; Urbanska, Paulina ; Joachimiak, Ewa ; Lin, Jianfeng ; Wloga, Dorota ; Nicastro, Daniela. / The I1 dynein-associated tether and tether head complex is a conserved regulator of ciliary motility. In: Molecular Biology of the Cell. 2018 ; Vol. 29, No. 9. pp. 1048-1059.
@article{48b68f051fcf4d16a642a530507bc445,
title = "The I1 dynein-associated tether and tether head complex is a conserved regulator of ciliary motility",
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.",
author = "Gang Fu and Qian Wang and Nhan Phan and Paulina Urbanska and Ewa Joachimiak and Jianfeng Lin and Dorota Wloga and Daniela Nicastro",
year = "2018",
month = "5",
day = "1",
doi = "10.1091/mbc.E18-02-0142",
language = "English (US)",
volume = "29",
pages = "1048--1059",
journal = "Molecular Biology of the Cell",
issn = "1059-1524",
publisher = "American Society for Cell Biology",
number = "9",

}

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

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.

UR - http://www.scopus.com/inward/record.url?scp=85047368066&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85047368066&partnerID=8YFLogxK

U2 - 10.1091/mbc.E18-02-0142

DO - 10.1091/mbc.E18-02-0142

M3 - Article

VL - 29

SP - 1048

EP - 1059

JO - Molecular Biology of the Cell

JF - Molecular Biology of the Cell

SN - 1059-1524

IS - 9

ER -