Abstract
The haploid germ cell-specific Tektin-t protein is a member of the Tektin family of proteins that form filaments in flagellar, ciliary, and axonemal microtubules. To investigate the physiological role of Tektin-t, we generated mice with a mutation in the tektin-t gene. The homozygous mutant males were infertile, while the females were fully fertile. Sperm morphology and function were abnormal, with frequent bending of the sperm flagella and marked defects in motility. In vitro fertilization assays showed that the defective spermatozoa were able to fertilize eggs. Electron microscopic examination showed that the dynein inner arm structure was disrupted in the sperm flagella of tektin-t-deficient mice. Furthermore, homozygous mutant mice had functionally defective tracheal cilia, as evidenced by altered dynein arm morphology. These results indicate that Tektin-t participates in dynein inner arm formation or attachment and that the loss of Tektin-t results in impaired motility of both flagella and cilia. Therefore, the tektin-t gene is one of the causal genes for immotile-cilium syndrome/primary ciliary dyskinesia.
MeSH Terms
Animals
Cilia/physiology
Ciliary Motility Disorders/etiology,genetics,physiopathology
Dyneins/chemistry,physiology
Female
Fertilization in Vitro
Infertility, Male/etiology,genetics,physiopathology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Microscopy, Electron
Microtubule Proteins/deficiency,genetics,physiology
Sperm Motility/genetics,physiology
Sperm Tail/physiology,ultrastructure
Chemicals
Microtubule Proteins
tektins
Dyneins
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Tanaka Hiromitsu
Department of Science for Laboratory Animal Experimentation, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
[email protected]
Iguchi Naoko
Toyama Yoshiro
Kitamura Kouichi
Takahashi Tohru
Kaseda Kazuhiro
Maekawa Mamiko
Nishimune Yoshitake
References (33)
33 references, click to expand
-
Biochemical characterization of tektins from sperm flagellar doublet microtubules.
J Cell Biol. 1987 Apr;104(4):1069-75
PMID: 3558479
-
Microtubule-associated proteins.
Annu Rev Cell Biol. 1986;2:421-57
PMID: 3548773
-
Evidence for tektins in centrioles and axonemal microtubules.
Proc Natl Acad Sci U S A. 1988 Apr;85(8):2643-7
PMID: 3282233
-
Structure and utilization of tubulin isotypes.
Annu Rev Cell Biol. 1988;4:687-716
PMID: 3058169
-
Retention of ciliary ninefold structure after removal of microtubules.
J Cell Sci. 1989 Mar;92 ( Pt 3):391-402
PMID: 2592445
-
Role of tubulin and dynein in spermatozoan motility.
Mol Reprod Dev. 1993 Oct;36(2):221-3
PMID: 8257571
-
The Rib43a protein is associated with forming the specialized protofilament ribbons of flagellar microtubules in Chlamydomonas.
Mol Biol Cell. 2000 Jan;11(1):201-15
PMID: 10637302
-
The spatial and temporal expression of Tekt1, a mouse tektin C homologue, during spermatogenesis suggest that it is involved in the development of the sperm tail basal body and axoneme.
Eur J Cell Biol. 2000 Oct;79(10):718-25
PMID: 11089920
-
Disruption of an inner arm dynein heavy chain gene results in asthenozoospermia and reduced ciliary beat frequency.
Hum Mol Genet. 2001 May 15;10(11):1117-28
PMID: 11371505
-
Cloning and characterization of a novel human TEKTIN1 gene.
Int J Biochem Cell Biol. 2001 Dec;33(12):1172-82
PMID: 11606253
-
Tektin B1 demonstrates flagellar localization in human sperm.
Biol Reprod. 2002 Jan;66(1):241-50
PMID: 11751288
-
Loss of function of axonemal dynein Mdnah5 causes primary ciliary dyskinesia and hydrocephalus.
Hum Mol Genet. 2002 Mar 15;11(6):715-21
PMID: 11912187
-
Cloning and characterization of the human tektin-t gene.
Mol Hum Reprod. 2002 Jun;8(6):525-30
PMID: 12029069
-
Cloning and characterization of testis-specific tektin in Bombyx mori.
Comp Biochem Physiol B Biochem Mol Biol. 2002 Nov;133(3):371-82
PMID: 12431405
-
Tektins are heterodimeric polymers in flagellar microtubules with axial periodicities matching the tubulin lattice.
J Biol Chem. 1994 Dec 16;269(50):31800-6
PMID: 7527396
-
At least one of the protofilaments in flagellar microtubules is not composed of tubulin.
Curr Biol. 1995 Feb 1;5(2):158-67
PMID: 7743179
-
Dynein inner arm heavy chain identification in cAMP-activated flagella using class-specific polyclonal antibodies.
Cell Motil Cytoskeleton. 1995;30(4):261-71
PMID: 7796457
-
Structural comparison of tektins and evidence for their determination of complex spacings in flagellar microtubules.
J Mol Biol. 1996 Mar 29;257(2):385-97
PMID: 8609631
-
Disruption of overlapping transcripts in the ROSA beta geo 26 gene trap strain leads to widespread expression of beta-galactosidase in mouse embryos and hematopoietic cells.
Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3789-94
PMID: 9108056
-
A critical review of the physiological importance and analysis of sperm movement in mammals.
Hum Reprod Update. 1997 Sep-Oct;3(5):403-39
PMID: 9528908
-
Disruption and sequence identification of 2,000 genes in mouse embryonic stem cells.
Nature. 1998 Apr 9;392(6676):608-11
PMID: 9560157
-
Expression of ciliary tektins in brain and sensory development.
J Neurosci. 1998 Nov 1;18(21):8912-8
PMID: 9786996
-
Molecular cloning of haploid germ cell-specific tektin cDNA and analysis of the protein in mouse testis.
FEBS Lett. 1999 Aug 6;456(2):315-21
PMID: 10456331
-
Cilia are at the heart of vertebrate left-right asymmetry.
Curr Opin Genet Dev. 2003 Aug;13(4):385-92
PMID: 12888012
-
Sperm pathology: a step beyond descriptive morphology. Origin, characterization and fertility potential of abnormal sperm phenotypes in infertile men.
Hum Reprod Update. 2003 Sep-Oct;9(5):405-28
PMID: 14640375
-
Protofilament ribbon compartments of ciliary and flagellar microtubules.
Protist. 2003 Oct;154(3-4):299-311
PMID: 14658491
-
A tektin homologue is decreased in chlamydomonas mutants lacking an axonemal inner-arm dynein.
Mol Biol Cell. 2004 May;15(5):2105-15
PMID: 14978211
-
A human syndrome caused by immotile cilia.
Science. 1976 Jul 23;193(4250):317-9
PMID: 1084576
-
Cilia and flagella of eukaryotes.
J Cell Biol. 1981 Dec;91(3 Pt 2):107s-124s
PMID: 6459326
-
Tektin filaments: chemically unique filaments of sperm flagellar microtubules.
Prog Clin Biol Res. 1982;80:127-32
PMID: 6212936
-
Structure and chemical composition of insoluble filamentous components of sperm flagellar microtubules.
J Cell Sci. 1982 Dec;58:1-22
PMID: 7183681
-
Localization of tektin filaments in microtubules of sea urchin sperm flagella by immunoelectron microscopy.
J Cell Biol. 1985 Jan;100(1):126-35
PMID: 3880749
-
Studies of tektin filaments from flagellar microtubules by immunoelectron microscopy.
J Cell Sci Suppl. 1986;5:55-68
PMID: 3308918