Male infertility-associated Ccdc108 regulates multiciliogenesis via the intraflagellar transport machinery

Author:

Zhao, Huijie

Sun,Jian

Insinna, Christine

Lu,Quanlong

Wang, Ziqiu

Nagashima,Kunio

Stauffer,Jimmy

Andresson,Thorkell

Specht,Suzanne

Perera, Sumeth

Daar,Ira [ORCID]

Westlake,Christopher [ORCID]
Author Address

Laboratory of Cellular and Developmental Signaling, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA., Cancer & Developmental Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA., Cancer Research Technology Program, Electron Microscopy Laboratory, Frederick National Laboratory for Cancer Research (FNLCR), Leidos Biomedical Research Inc., Frederick, MD, USA., Protein Characterization Laboratory (PCL) Mass Spectrometry Center, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.,

Abstract:

Motile cilia on the cell surface generate movement and directional fluid flow that is crucial for various biological processes. Dysfunction of these cilia causes human diseases such as sinopulmonary disease and infertility. Here, we show that Ccdc108, a protein linked to male infertility, has an evolutionarily conserved requirement in motile multiciliation. Using?Xenopus laevis?embryos, Ccdc108 is shown to be required for the migration and docking of basal bodies to the apical membrane in epidermal multiciliated cells (MCCs). We demonstrate that Ccdc108 interacts with the IFT-B complex, and the ciliation requirement for Ift74 overlaps with Ccdc108 in MCCs. Both Ccdc108 and IFT-B proteins localize to migrating centrioles, basal bodies, and cilia in MCCs. Importantly, Ccdc108 governs the centriolar recruitment of IFT while IFT licenses the targeting of Ccdc108 to the cilium. Moreover, Ccdc108 is required for the centriolar recruitment of Drg1 and activated RhoA, factors that help establish the apical actin network in MCCs. Together, our studies indicate that Ccdc108 and IFT-B complex components cooperate in multiciliogenesis. Published 2022. This article is a U.S. Government work and is in the public domain in the USA. Published under the terms of the CC BY NC ND 4.0 license.

See More

Author Address