首页|Adenylate kinase phosphate energy shuttle underlies energetic communication in flagellar axonemes

Adenylate kinase phosphate energy shuttle underlies energetic communication in flagellar axonemes

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The complexities of energy transfer mechanisms in the flagella of mammalian sperm flagella have been intensively investigated and de-monstrate 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.

adenylate kinaseSubgroup Ⅲ AKsAK8AK9male infertilityATP transferradial spoke

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

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Reproductive Medicine Center,Department of Obstetrics and Gynecology,the First Affiliated Hospital of Anhui Medical University,Hefei 230022,China

NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract(Anhui Medical University),Hefei 230032,China

Key Laboratory of Population Health Across Life Cycle(Anhui Medical University),Ministry of Education of the People's Republic of China,Hefei 230032,China

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

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

Reproductive Medicine Center,Department of Obstetrics and Gynecology,The First Affiliated Hospital of Anhui Medical University,Hefei 230022,China

Anhui Province Key Laboratory of Reproductive Health and Genetics,Hefei 230032,China

Biopreservation and Artificial Organs,Anhui Provincial Engineering Research Center,Anhui Medical University,Hefei 230032,China

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

Reproductive Medicine Center,Department of Obstetrics and Gynecology,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200080,China

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National Key Research and Development Program of ChinaNational Key Research and Development Program of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaUniversity Outstanding Young Talents Support ProgramNonprofit Central Research Institute Fund of Chinese Academy of Medical Sciences

2022YFC27027022021YFC2700901819714418217160732000584gxyq20211742019PT310002

2024

中国科学:生命科学(英文版)
中国科学院

中国科学:生命科学(英文版)

CSTPCD
影响因子:0.806
ISSN:1674-7305
年,卷(期):2024.67(8)