TEKT1

TEKT1 encodes a tektin family protein that serves as an essential structural component of the tektin bundle within doublet microtubules of motile cilia and sperm flagella. TEKT1 is transiently associated with the centrosome/basal body during flagellar nucleation in spermatids and subsequently localizes along the axoneme, where its proper distribution depends on TBC1D21-mediated transport; loss of TBC1D21 causes aberrant TEKT1 accumulation in the sperm midpiece (PMID:11089920, PMID:38822685). TEKT1 knockout mice are male-infertile due to impaired sperm motility and disassembly of the tektin bundle, and biallelic TEKT1 mutations in humans cause severe motile cilia dysmotility in airway epithelial cells without major ultrastructural defects, establishing that TEKT1 is required for motile ciliary function beyond spermatogenesis (PMID:41764189, PMID:29121203). TEKT1 mRNA is post-transcriptionally regulated by miR-199-5p, and its suppression disrupts flagellar assembly and causes spermatid apoptosis (PMID:35418106).

1. 2000 Medium

   The first subcellular localization of TEKT1 revealed its transient association with the centrosome of round spermatids, establishing that it participates early in flagellar axoneme nucleation rather than acting solely as a late structural component.

   Evidence Immunofluorescence co-localization with centrosome marker ANA and in situ hybridization in mouse testis sections

   PMID:11089920

   Open questions at the time

   • No loss-of-function data to confirm a functional requirement at the centrosome
   • Mechanism of TEKT1 recruitment to and departure from the centrosome unknown
2. 2018 High

   Patient-derived biallelic TEKT1 mutations and zebrafish knockdown demonstrated that TEKT1 is required for motile cilia beat function—not only sperm flagella—and showed genetic interaction with the intraflagellar transport component WDR19, placing TEKT1 in a broader ciliary assembly pathway.

   Evidence Immunofluorescence in patient airway cells and cycling cells; zebrafish tekt1 morpholino knockdown with live motility imaging; genetic epistasis with wdr19

   PMID:29121203

   Open questions at the time

   • Structural basis of motility defect without ultrastructural changes is unexplained
   • Nature of TEKT1–WDR19 functional relationship (direct or indirect) not resolved
3. 2022 Medium

   Identification of miR-199-5p as a direct post-transcriptional regulator of TEKT1 mRNA revealed that TEKT1 expression levels must be tightly controlled for normal flagellar assembly, as its suppression causes spermatid apoptosis and flagellar defects.

   Evidence Luciferase reporter assay for miR-199-5p/Tekt1 3′UTR; in vivo agomir/antagomir injection in diploid red crucian carp

   PMID:35418106

   Open questions at the time

   • Relevance of miR-199-5p regulation to mammalian spermatogenesis not tested
   • Whether other miRNAs also regulate TEKT1 is unknown
4. 2023 Medium

   TEKT1 promoter-driven reporter expression in primate ES cells marked multiciliated epithelial-like cells bearing 9+2 motile cilia, confirming TEKT1 as a conserved marker of multiciliated cell identity beyond the germline.

   Evidence Venus reporter under TEKT1 promoter in cynomolgus monkey ES cells; transmission electron microscopy confirming 9+2 architecture

   PMID:37186436

   Open questions at the time

   • Functional requirement of TEKT1 in ES-derived multiciliated cells not tested by loss-of-function
   • Whether TEKT1 contributes to multiciliogenesis or is only a late differentiation marker is unclear
5. 2024 Medium

   Physical interaction between TBC1D21 and TEKT1, combined with mislocalization of TEKT1 in Tbc1d21-null sperm, established that axonemal TEKT1 distribution is actively regulated by a Rab-associated transport mechanism during sperm tail assembly.

   Evidence Co-immunoprecipitation; comparative proteomics of WT vs. Tbc1d21-KO mouse sperm; immunofluorescence co-localization with RAB10

   PMID:38822685

   Open questions at the time

   • Whether TBC1D21 GAP activity toward a specific Rab is the operative mechanism remains untested
   • Whether this transport pathway operates in motile cilia of non-sperm cells is unknown
6. 2025 Low

   A reported interaction between TEKT1 and AMPK-γ in endometrial cancer cells linked TEKT1 to fatty acid synthesis and cancer cell proliferation, but this finding stands outside the established ciliary/flagellar context and lacks mechanistic follow-up.

   Evidence Co-immunoprecipitation and Western blot in endometrial cancer cell lines with overexpression phenotypes

   PMID:39794059

   Open questions at the time

   • Single Co-IP without reciprocal validation or domain mapping
   • No evidence TEKT1 is normally expressed in endometrial tissue at physiologically meaningful levels
   • No in vivo validation of the AMPK interaction
7. 2026 High

   TEKT1 knockout mice provided definitive evidence that TEKT1 is an essential structural subunit of the tektin bundle within axonemal doublet microtubules, and its loss defines a distinct asthenozoospermia subtype through complete loss of sperm motility.

   Evidence Gene knockout mouse; sperm motility analysis; high-resolution structural analysis of doublet microtubules

   PMID:41764189

   Open questions at the time

   • Precise position of TEKT1 within the tektin filament relative to TEKT2–5 not resolved at atomic resolution
   • Whether TEKT1 loss in mice also recapitulates airway cilia dysfunction (as seen in human patients) was not reported

• It remains unknown how TEKT1 is assembled into the tektin bundle at atomic resolution, what specific intraflagellar transport adaptors deliver TEKT1 to its axonemal position, and whether TEKT1 mutations constitute a bona fide primary ciliary dyskinesia locus in humans.
• No high-resolution structure of TEKT1 or the tektin bundle exists
• Relationship between TEKT1 and IFT machinery beyond genetic interaction with WDR19 is uncharacterized
• Human genetic confirmation of TEKT1 as a primary ciliary dyskinesia gene in larger cohorts is lacking