Role of intraflagellar transport protein IFT140 in the formation and function of motile cilia in mammals

Yi Tian Yap, Jiehong Pan, Jian Xu, Shuo Yuan, Changmin Niu, Cheng Zheng, Wei Li, Ting Zhou, Tao Li, Yong Zhang, Michael J. Holtzman, Gregory J. Pazour, Rex A. Hess, Christopher V. Kelly, Aminata Touré, Steven Brody, Zhibing Zhang

Research output: Contribution to journalArticlepeer-review

Abstract

Cilia are microtubular structures extending from the surface of most mammalian cells. They can be categorized as motile cilia and primary sensory cilia. Both types possess intraflagellar transport (IFT) machinery, composed of unique protein complexes that travel along the microtubules to deliver proteins for ciliary and flagellar assembly, disassembly, and homeostasis. Although the role of IFT in primary cilia formation has been well studied, little is known about its role in mammalian motile cilia assembly. We generated conditional knockout mice by breeding floxed Ift140 mice with the FOXJ1-Cre transgenic mouse line to specifically delete Ift140 from cells that assemble motile cilia. Mice with Ift140 deficiency did not have laterality defects or gross; however most died prior to sexual maturity. Those mutants that survived to adulthood were completely infertile. Males demonstrated abnormal spermatogenesis associated with reduced sperm count and motility, together with short length flagella, and abnormal morphology. Cilia length was diminished in the epithelial cells of the efferent ductules and airways. Cilia from cultured tracheal epithelial cells were also short and had reduced beat frequency (CBF). Ultrastructural studies revealed the presence of inner and outer dynein arms, but an abnormal central apparatus, and the accumulation of particles within the cilia. Overall, the short length and abnormal localization of ciliary proteins in Ift140 conditional mutants resulted in inadequate cilia function despite proper localization of the dynein motor complexes. We propose a key role of Ift140 for motile cilia assembly in certain tissues and suggest that genetic alterations of IFT140 could be associated with motile ciliopathies.

Original languageEnglish
Pages (from-to)198
Number of pages1
JournalCellular and Molecular Life Sciences
Volume82
Issue number1
DOIs
StatePublished - May 10 2025

Keywords

  • Cilia
  • Fertility
  • Intraflagellar transport
  • Sperm

Fingerprint

Dive into the research topics of 'Role of intraflagellar transport protein IFT140 in the formation and function of motile cilia in mammals'. Together they form a unique fingerprint.

Cite this