Absence of tektin 4 causes asthenozoospermia and subfertility in male mice.
Sperm flagellar motion is the outcome of a dynamic interplay between the axonemal cytoskeleton, the peri-axonemal accessory structures, and multiple regulatory networks that coordinate to produce flagellar beat and waveform. Tektins are conserved components of the flagellar proteome in evolutionarily diverse species and are believed to play essential roles in the mechanics of sperm motility. Using database mining, we identified multiple new paralogs of previously annotated tektins, including tektin 4 (TEKT4), which shares 77.1% identity with its nearest human homologue. Mouse Tekt4 is a germ cell-enriched gene, most abundantly expressed in haploid round spermatids in the testis, and the protein is localized to the sperm flagella. Male mice lacking TEKT4 on a 129S5/SvEvBrd inbred background are subfertile. Tekt4-null sperm exhibit drastically reduced forward progressive velocity and uncoordinated waveform propagation along the flagellum. In Tekt4-null sperm, flagellar ultrastructure is grossly unaltered as revealed by transmission electron microscopy. However, the ineffective flagellar strokes lead to approximately 10-fold higher consumption of intracellular ATP in Tekt4-null sperm as compared to wild-type, and null spermatozoa rapidly lose progressive motility when incubated for > or = 1.5 h. Our studies demonstrate that TEKT4 is necessary for the proper coordinated beating of the sperm flagellum and male reproductive physiology.
Roy
Angshumoy
A
Department of Pathology, One Baylor Plaza, Baylor College of Medicine, Houston, Texas 77030, USA.
Lin
Yi-Nan
YN
Agno
Julio E
JE
DeMayo
Francesco J
FJ
Matzuk
Martin M
MM
D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D053627:Asthenozoospermia / Q000235:genetics* / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000502:physiology*; D003599:Cytoskeleton / Q000378:metabolism; D005407:Flagella / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008868:Microtubule Proteins / Q000235:genetics* / Q000502:physiology*; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D013094:Spermatozoa / Q000378:metabolism
D003598:Cytoskeletal Proteins; D008868:Microtubule Proteins; C044103:tektins; D000255:Adenosine Triphosphate