CCDC189 affects sperm flagellum formation by interacting with CABCOC01  

作　　者：Mengyue Wang Junyan Kang Zhiming Shen Yingchun Hu Min Chen Xiuhong Cui Hongbin Liu Fei Gao 

机构地区：[1]State Key Laboratory of Stem Cell and Reproductive Biology,Institute of Zoology,Chinese Academy of Sciences,Beijing 100020,China [2]Institute for Stem Cell and Regeneration,Chinese Academy of Sciences,Beijing 100020,China [3]Beijing Institute for Stem Cell and Regenerative Medicine,Beijing 100020,China [4]University of Chinese Academy of Sciences,Beijing 101499,China [5]Department of Ophthalmology,Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology,Shanghai 200031,China [6]Core Facilities,College of Life Sciences,Peking University,Beijing 100871,China [7]Center for Reproductive Medicine,Shandong University,Jinan 250100,China

出　　处：《National Science Review》2023年第9期174-183,共10页国家科学评论（英文版）

基　　金：supported by the National Key R&D Program of China(2022YFC2702400);the National Natural Science Foun-dation of China(32270902,31970785 and 32170855);the Faculty Resources Project of the College of Life Sciences,Inner Mongolia University(2022-104).

摘　　要：Multiple morphological abnormalities of the sperm flagella(MMAF)are one of the major causes of male infertility and are characterized by multiple defects.In this study,we found that the coiled-coil domain-containing 189(Ccdc189)gene was predominantly expressed in mouse testes and that inactivation of the Ccdc189 gene caused male infertility.Histological studies revealed that most sperm from Ccdc189-deficient mice carried coiled,curved or short flagell a,which are typical MMAF phenotypes.Immunoelectron microscopy showed that the CCDC189 protein was located at the radial spoke of the first peripheral microtubule doublet in the sperm axoneme.A CCDC189-interacting protein,CABCOCO1(ciliary-associated calcium-binding coiled-coil protein 1),was discovered via co-immunoprecipitation and mass spectrometry,and inactivation of Cabcocol caused malformation of sperm flagell a,which was consistent with findings obtained with Ccdc189-deficient mice.Further studies revealed that inactivation of CCDC189 caused downregulation of CABCOCO1 protein expression and that both CCDC189 and CABCOCO1 interacted with the radial-spoke-specific protein RSPH1 and intraflagellar transport proteins.This study demonstrated that Ccdc189 is a radial-spoke-associated protein and is involved in sperm flagellum formation through its interactions with CABCOCO1 and intraflagellar transport proteins.

关 键 词：MMAF Ccdc189 Cabcoco1 flagellum formation radial spoke 

分 类 号：R698.2[医药卫生—泌尿科学]