CFAP65 is essential for C2a projection integrity in axonemes: implications for organ-specific ciliary dysfunction and infertility.

ABSTRACT: Defects in motile cilia and flagella lead to motile ciliopathies, including primary ciliary dyskinesia (PCD), which manifests as multi-organ dysfunction such as hydrocephalus, infertility, and respiratory issues. CFAP65 variants are a common cause of male infertility, but its localization and function have remained unclear. In this study, we systematically evaluated CFAP65's role using Cfap65 knockout mice and human patients with CFAP65 variants. The knockout mice displayed severe sperm flagellar defects (MMAF), high hydrocephalus incidence, but no significant impact on respiratory cilia. Similarly, the patients exhibited MMAF and infertility without respiratory symptoms. CFAP65 was found to anchor at the base of the C2a projection of the axoneme, interacting with proteins such as CFAP70 a

SUBMITTER: Chen J 

PROVIDER: S-EPMC11759756 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature