Adenylate kinase phosphate energy shuttle underlies energetic communication in flagellar axonemes  

作　　者：Huan Wu Yanman Zhang Yuqian Li Shuya Sun Jintao Zhang Qingsong Xie Yue Dong Shushu Zhou Xuan Sha Kuokuo Li Jinyi Chen Xin Zhang Yang Gao Qunshan Shen Guanxiong Wang Xiaomin Zha Zongliu Duan Dongdong Tang Chuan Xu Hao Geng Mingrong Lv Yuping Xu Ping Zhou Zhaolian Wei Rong Hua Yunxia Cao Mingxi Liu Xiaojin He 

机构地区：[1]Reproductive Medicine Center,Department of Obstetrics and Gynecology,The First Affiliated Hospital of Anhui Medical University,Hefei 230022,China [2]State Key Laboratory of Reproductive Medicine and Offspring Health,Department of Histology and Embryology,School of Basic Medical Sciences,Nanjing Medical University,Nanjing 210029,China [3]State Key Laboratory of Reproductive Medicine and Offspring Health,The Affiliated Taizhou People’s Hospital of Nanjing Medical University,Taizhou School of Clinical Medicine,Nanjing Medical University,Nanjing 211166,China [4]Reproductive Medicine Center,Department of Obstetrics and Gynecology,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200080,China [5]State Key Laboratory of Reproductive Medicine and Offspring Health,Clinical Center of Reproductive Medicine,The First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China [6]NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract(Anhui Medical University),Hefei 230032,China [7]Key Laboratory of Population Health Across Life Cycle(Anhui Medical University),Ministry of Education of the People’s Republic of China,Hefei 230032,China [8]Anhui Province Key Laboratory of Reproductive Health and Genetics,Hefei 230032,China [9]Biopreservation and Artificial Organs,Anhui Provincial Engineering Research Center,Anhui Medical University,Hefei 230032,China

出　　处：《Science China(Life Sciences)》2024年第8期1697-1714,共18页中国科学（生命科学英文版）

基　　金：supported by National Key Research and Development Program of China(2022YFC2702702,2021YFC2700901);the National Natural Science Foundation of China(81971441,82171607,32000584);the University Outstanding Young Talents Support Program(gxyq2021174);Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2019PT310002);Anhui Provincial Natural Science Foundation(2208085Y31);the Natural Science Foundation of Jiangsu Province(BK20230004).

摘　　要：The complexities of energy transfer mechanisms in the flagella of mammalian sperm flagella have been intensively investigated and demonstrate significant diversity across species.Enzymatic shuttles,particularly adenylate kinase(AK)and creatine kinase(CK),are pivotal in the efficient transfer of intracellular ATP,showing distinct tissue-and species-specificity.Here,the expression profiles of AK and CK were investigated in mice and found to fall into four subgroups,of which Subgroup III AKs were observed to be unique to the male reproductive system and conserved across chordates.Both AK8 and AK9 were found to be indispensable to male reproduction after analysis of an infertile male cohort.Knockout mouse models showed that AK8 and AK9 were central to promoting sperm motility.Immunoprecipitation combined with mass spectrometry revealed that AK8 and AK9 interact with the radial spoke(RS)of the axoneme.Examination of various human and mouse sperm samples with substructural damage,including the presence of multiple RS subunits,showed that the head of radial spoke 3 acts as an adapter for AK9 in the flagellar axoneme.Using an ATP probe together with metabolomic analysis,it was found that AK8 and AK9 cooperatively regulated ATP transfer in the axoneme,and were concentrated at sites associated with energy consumption in the flagellum.These findings indicate a novel function for RS beyond its structural role,namely,the regulation of ATP transfer.In conclusion,the results expand the functional spectrum of AK proteins and suggest a fresh model regarding ATP transfer within mammalian flagella.

关 键 词：adenylate kinase Subgroup III AKs AK8 AK9 male infertility ATP transfer radial spoke 

分 类 号：Q78[生物学—分子生物学]