期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 114, 期 27, 页码 E5370-E5378出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1621279114
关键词
male infertility; asthenozoospermia; glycolysis; mutant mouse; testis-specific gene
资金
- National Key Research and Development Program of China [2016YFA0500903]
- National Basic Research Program of China [2015CB943003]
- Natural Science Foundation of China [31530047, 31571536]
- Eunice Kennedy Shriver National Institute of Child Health and Human Development [R01 HD088412]
- Osaka University International Joint Research Promotion Program
- Ministry of Education, Culture, Sports, Science, and Technology [JP25112007]
- Takeda Science Foundation
- Baylor College of Medicine [5T32HD007165-35]
- Academy of Finland
- Sigrid Juselius Foundation
- Wellcome Trust [079643, 098051]
- National Institutes of Health [Knockout Mouse Project (KOMP)] Award [U01-HG004080]
- Grants-in-Aid for Scientific Research [15K21737, 16H06276, 17H04987, 25112007] Funding Source: KAKEN
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.
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