Julio M. Castaneda, Rong Hua, Haruhiko Miyata, Asami Oji, Yueshuai Guo, Yiwei Cheng, Tao Zhou, Xuejiang Guo, Yiqiang Cui, Bin Shen, Zibin Wang, Zhibin Hu, Zuomin Zhou, Jiahao Sha, Renata Prunskaite-Hyyrylainen, Zhifeng Yu, Ramiro Ramirez-Solis, Masahito Ikawa, Martin M. Matzuk, Mingxi Liu, Tcte1 is required for male mouse fertility. Proceedings of the National Academy of Sciences Jul 2017, 114 (27) E5370-E5378; DOI: 10.1073/pnas.1621279114
TCTE1 is a conserved component of the dynein regulatory complex and is required for motility and metabolism in mouse spermatozoa
|Author:||Castaneda, Julio M.1,2; Hua, Rong3,4; Miyata, Haruhiko2;|
1Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030
2Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 5650871, Japan
3State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, People’s Republic of China
4Department of Histology and Embryology, Nanjing Medical University, Nanjing 210029, People’s Republic of China
5Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 5650871, Japan
6Animal Core Facility of Nanjing Medical University, Nanjing 210029, People’s Republic of China
7Center for Reproductive Medicine, Baylor College of Medicine, Houston, TX 77030
8Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu FI-90014, Finland
9Center for Drug Discovery, Baylor College of Medicine, Houston, TX 77030
10Wellcome Trust Sanger Institute, Hinxton CB10 1SA, United Kingdom
11The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 1088639, Japan
12Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030
13Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030
14Department of Pharmacology, Baylor College of Medicine, Houston, TX 77030
|Online Access:||PDF Full Text (PDF, 2.1 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2019062621978
National Academy of Sciences of the United States of America,
|Publish Date:|| 2019-06-26
Flagella and cilia are critical cellular organelles that provide a means for cells to sense and progress through their environment. The central component of flagella and cilia is the axoneme, which comprises the “9+2” microtubule arrangement, dynein arms, radial spokes, and the nexin-dynein regulatory complex (N-DRC). Failure to properly assemble components of the axoneme leads to defective flagella and in humans leads to a collection of diseases referred to as ciliopathies. Ciliopathies can manifest as severe syndromic diseases that affect lung and kidney function, central nervous system development, bone formation, visceral organ organization, and reproduction. T-Complex-Associated–Testis-Expressed 1 (TCTE1) is an evolutionarily conserved axonemal protein present from Chlamydomonas (DRC5) to mammals that localizes to the N-DRC. Here, we show that mouse TCTE1 is testis-enriched in its expression, with its mRNA appearing in early round spermatids and protein localized to the flagellum. TCTE1 is 498 aa in length with a leucine rich repeat domain at the C terminus and is present in eukaryotes containing a flagellum. Knockout of Tcte1 results in male sterility because Tcte1-null spermatozoa show aberrant motility. Although the axoneme is structurally normal in Tcte1 mutant spermatozoa, Tcte1-null sperm demonstrate a significant decrease of ATP, which is used by dynein motors to generate the bending force of the flagellum. These data provide a link to defining the molecular intricacies required for axoneme function, sperm motility, and male fertility.
Proceedings of the National Academy of Sciences of the United States of America
|Pages:||E5370 - E5378|
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
1182 Biochemistry, cell and molecular biology
This work was supported by the National Key Research and Development Program of China (2016YFA0500903); the National Basic Research Program of China (2015CB943003); the Natural Science Foundation of China (31530047 and 31571536); Eunice Kennedy Shriver National Institute of Child Health and Human Development Grant R01 HD088412 (to M.M.M. and M.I.); the Osaka University International Joint Research Promotion Program (to M.M.M. and M.I.); Ministry of Education, Culture, Sports, Science, and Technology KAKENHI Grant JP25112007 (to M.I.); the Takeda Science Foundation Grant (to H.M. and M.I); Baylor College of Medicine Training Grant 5T32HD007165-35 (to J.M.C.); the Academy of Finland and the Sigrid Juselius Foundation (to R.P.-H.); Wellcome Trust Grants 079643 and 098051 (to R.R.-S.); and National Institutes of Health [Knockout Mouse Project (KOMP)] Award U01-HG004080 (to R.R.-S.).
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1621279114/-/DCSupplemental.
© The Authors, 2017. Freely available online through the PNAS open access option.