Proceedings of the National Academy of Sciences - PNAS, 2017-07, Vol.114 (27), p.E5370-E5378
2017
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- Autor(en) / Beteiligte
- Titel
- TCTE1 is a conserved component of the dynein regulatory complex and is required for motility and metabolism in mouse spermatozoa
- Ist Teil von
- Proceedings of the National Academy of Sciences - PNAS, 2017-07, Vol.114 (27), p.E5370-E5378
- Ort / Verlag
- United States: National Academy of Sciences
- Erscheinungsjahr
- 2017
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0027-8424eISSN: 1091-6490DOI: 10.1073/pnas.1621279114Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5502601
- Format
- –
- Schlagworte
- Aberration, Adenosine Triphosphate - metabolism, Animals, Axoneme - metabolism, Biological Sciences, Bone growth, Central nervous system, Chlamydomonas - metabolism, Cilia, Cilia - metabolism, Crosses, Genetic, Cytoskeleton - metabolism, Developmental biology, Dynein, Dyneins - metabolism, Eukaryotes, Female, Fertility, Flagella, Flagella - metabolism, Gene expression, Green Fluorescent Proteins - metabolism, HEK293 Cells, Homozygote, Humans, Infertility, Leucine, Lung diseases, Male, Male sterility, Mens health, Metabolism, Mice, Microtubules - metabolism, Motors, mRNA, Mutation, Nexin, Organelles, Osteogenesis, PNAS Plus, Proteins, Proteins - genetics, Proteins - physiology, Rodents, Sperm, Sperm Motility, Spermatids, Spermatids - metabolism, Spermatozoa, Spermatozoa - physiology, Spokes, Testis - metabolism