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Proc Natl Acad Sci U S A. 2017 Jul 3;114(27):E5370-E5378. doi: 10.1073/pnas.1621279114. Epub 2017 Jun 19.

TCTE1 is a conserved component of the dynein regulatory complex and is required for motility and metabolism in mouse spermatozoa.

Castaneda JM1,2, Hua R3,4, Miyata H2, Oji A2,5, Guo Y3,4, Cheng Y3,4, Zhou T3,4, Guo X3,4, Cui Y3,4, Shen B3, Wang Z3, Hu Z3,6, Zhou Z3,4, Sha J3,4, Prunskaite-Hyyrylainen R1,7,8, Yu Z1,9, Ramirez-Solis R10, Ikawa M11,5,12, Matzuk MM13,7,9,14,15,16, Liu M17,4.

Author information

1
Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030.
2
Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 5650871, Japan.
3
State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, People's Republic of China.
4
Department of Histology and Embryology, Nanjing Medical University, Nanjing 210029, People's Republic of China.
5
Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 5650871, Japan.
6
Animal Core Facility of Nanjing Medical University, Nanjing 210029, People's Republic of China.
7
Center for Reproductive Medicine, Baylor College of Medicine, Houston, TX 77030.
8
Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu FI-90014, Finland.
9
Center for Drug Discovery, Baylor College of Medicine, Houston, TX 77030.
10
Wellcome Trust Sanger Institute, Hinxton CB10 1SA, United Kingdom.
11
Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 5650871, Japan; mingxi.liu@njmu.edu.cn ikawa@biken.osaka-u.ac.jp mmatzuk@bcm.edu.
12
The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 1088639, Japan.
13
Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030; mingxi.liu@njmu.edu.cn ikawa@biken.osaka-u.ac.jp mmatzuk@bcm.edu.
14
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030.
15
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030.
16
Department of Pharmacology, Baylor College of Medicine, Houston, TX 77030.
17
State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, People's Republic of China; mingxi.liu@njmu.edu.cn ikawa@biken.osaka-u.ac.jp mmatzuk@bcm.edu.

Abstract

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.

KEYWORDS:

asthenozoospermia; glycolysis; male infertility; mutant mouse; testis-specific gene

PMID:
28630322
PMCID:
PMC5502601
DOI:
10.1073/pnas.1621279114
[Indexed for MEDLINE]
Free PMC Article

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