TEKT3

TEKT3 is a tektin family filamentous protein that functions in axonemal and acrosomal architecture of spermatozoa and in kinocilia maintenance of sensory hair cells. In sperm, TEKT3 assembles with other TEKTIN family members into a bundle stabilized by TEKTIP1; loss of TEKTIP1 primarily disrupts TEKT3 and its interactions with other tektins, leading to disorganized axoneme structures and reduced motility (PMID:38448737). TEKT3 also localizes to acrosomal structures and depends on CCDC38 for proper acrosomal targeting, with its mislocalization associated with acrosomal hypoplasia (PMID:26268136, PMID:37709195). Bi-allelic loss-of-function mutations in human TEKT3 cause oligoasthenoteratozoospermia with reduced progressive sperm motility and acrosomal hypoplasia (PMID:36708031).

1. 2004 Medium

   Initial cloning established TEKT3 as a testis-enriched tektin family member expressed in late spermatocytes and early spermatids, placing it temporally in the window of flagellar biogenesis.

   Evidence RT-PCR, Northern blot, and in situ hybridization in mouse testes

   PMID:14735490

   Open questions at the time

   • No functional data or loss-of-function phenotype at this stage
   • Protein-level localization within flagellar substructures not determined
   • No information on whether TEKT3 acts redundantly with other tektins
2. 2009 High

   Knockout studies demonstrated that TEKT3 is required for normal progressive sperm motility and flagellar architecture, and double-KO with TEKT4 revealed partial non-redundancy by causing subfertility beyond single-KO effects.

   Evidence Tekt3-null and Tekt3/Tekt4 double-null mice, sperm motility and ultrastructure analysis, fertility testing

   PMID:18951373

   Open questions at the time

   • Molecular mechanism of motility defect (dynein arm integrity, axonemal periodicity) not resolved
   • Whether TEKT3 interacts directly with TEKT4 or they stabilize the axoneme independently was unknown
3. 2015 Medium

   Proteomic identification of TEKT3 in the outer acrosomal membrane matrix expanded its known localization beyond the flagellum to the sperm head acrosomal compartment.

   Evidence MALDI-TOF-TOF proteomics, immunoprecipitation, and immunofluorescence in bovine sperm

   PMID:26268136

   Open questions at the time

   • Single species (bovine); conservation of acrosomal localization in human sperm not shown
   • Functional significance of acrosomal TEKT3 not tested
4. 2016 Medium

   Dynamic redistribution of TEKT3 from the post-acrosomal region to the equatorial segment during hyperactivation, and its loss during the acrosome reaction, linked TEKT3 to capacitation-associated membrane/cytoskeletal remodeling.

   Evidence Immunofluorescence in bull sperm under pharmacological hyperactivation and acrosome reaction conditions

   PMID:27883267

   Open questions at the time

   • Mechanism of TEKT3 translocation (phosphorylation, scaffolding) not identified
   • Functional consequence of preventing TEKT3 redistribution not tested
5. 2023 High

   Human genetic evidence established bi-allelic TEKT3 mutations as a cause of oligoasthenoteratozoospermia with acrosomal hypoplasia, and co-immunoprecipitation demonstrated TEKT3 forms a complex with other TEKTIN family proteins in human sperm.

   Evidence Whole-exome sequencing of infertile men, Sanger validation, Western blot, immunofluorescence, co-IP in human spermatozoa

   PMID:36708031

   Open questions at the time

   • Stoichiometry and architecture of the human TEKTIN complex not resolved
   • No structural data for TEKT3 or its disease-associated variants
6. 2023 Medium

   Epistasis experiments placed TEKT3 downstream of CCDC38 in acrosome biogenesis, showing that CCDC38 is required for TEKT3 protein levels and proper acrosomal localization.

   Evidence Ccdc38-knockout mice (base editing), Western blot and immunofluorescence of TEKT3 in sperm

   PMID:37709195

   Open questions at the time

   • Whether CCDC38 directly binds TEKT3 or acts indirectly is unknown
   • Single lab; no reciprocal rescue by TEKT3 overexpression tested
7. 2024 High

   Identification of TEKTIP1 as the primary stabilizer of TEKT3 within the tektin bundle clarified the molecular basis of axonemal tektin filament assembly: TEKTIP1 loss preferentially destabilizes TEKT3 and disrupts its interactions with other tektins.

   Evidence Tektip1-knockout mice, co-immunoprecipitation, cryo-EM-based localization, sperm motility and ultrastructure analysis

   PMID:38448737

   Open questions at the time

   • Atomic-resolution structure of the TEKTIP1–TEKT3 interface not determined
   • Whether TEKTIP1 acts as a chaperone during assembly or a structural brace in the mature filament is unresolved
8. 2025 Medium

   Extension to a non-reproductive context showed that TEKT3 maintains kinocilia integrity in zebrafish neuromast hair cells, with mutants displaying morphological defects, impaired mechanosensory function, and delayed hair cell regeneration — all rescued by wild-type mRNA.

   Evidence tekt3-mutant zebrafish, immunofluorescence, vital dye uptake, startle response assay, mRNA rescue

   PMID:40243732

   Open questions at the time

   • Whether mammalian TEKT3 has analogous ciliary roles outside the germline is untested
   • Molecular basis of kinocilia structural defect not characterized at the ultrastructural level
9. 2025 Medium

   A second Tekt3-KO mouse study found no significant fertility or motility defect, revealing strain- or condition-dependent penetrance of the loss-of-function phenotype and complicating the simple model of TEKT3 essentiality in mouse spermatogenesis.

   Evidence CRISPR/Cas9 knockout on C57BL/6 background, mating tests, sperm motility, histology

   PMID:41194443

   Open questions at the time

   • Discrepancy with earlier KO (PMID:18951373) not resolved — genetic background, housing conditions, or assay sensitivity differences not systematically tested
   • Whether compensatory upregulation of other tektins occurs in C57BL/6 background is unknown

• Key unresolved questions include the atomic structure of the TEKT3-containing tektin filament, the precise mechanism by which TEKT3 contributes to acrosome biogenesis versus axonemal integrity, and why TEKT3 loss in mice shows variable penetrance across genetic backgrounds.
• No high-resolution structure of TEKT3 or the tektin bundle
• Mechanism of TEKT3 involvement in acrosome formation remains indirect (downstream of CCDC38)
• Reconciliation of contrasting mouse KO phenotypes requires systematic background-controlled studies