TEKT1

TEKT1 (tektin-1) is a filament-forming structural protein of the tektin bundle within the doublet microtubules of sperm flagella and motile cilia, where it is required for axonemal structural integrity and ciliary/flagellar motility (PMID:41764189, PMID:29121203). During spermiogenesis it localizes transiently to the centrosome of round spermatids and then extends to the caudal end of elongating spermatids, consistent with a role in nucleating and building the flagellar axoneme (PMID:11089920), and in cycling cells and airway epithelium it marks centrosomes, basal bodies of primary and motile cilia, and the motile-cilium axoneme (PMID:29121203). Loss of function establishes its structural role: germline Tekt1 knockout in mice abolishes the tektin bundle within the doublet microtubule and causes asthenozoospermia-like male infertility, a phenotype not shared by Tekt5 knockout and thus reflecting functional divergence within the tektin family (PMID:41764189), while biallelic patient mutations impair its ciliary localization and produce severe motile-cilia motility defects, with a genetic interaction with the IFT-A subunit WDR19 (PMID:29121203). Its abundance and localization are controlled at two levels: post-transcriptional repression by miR-199-5p, which directly targets the Tekt1 3′UTR to restrain flagellar assembly (PMID:35418106), and physical interaction with TBC1D21, whose loss causes aberrant TEKT1 accumulation in the sperm midpiece, implicating TBC1D21 in directing TEKT1 within the axonemal transport system (PMID:38822685).

1. 2000 Medium

   Established when and where TEKT1 acts during sperm tail formation, linking it to early axoneme/basal body assembly rather than to a mature flagellar component alone.

   Evidence In situ hybridization and immunofluorescence with anti-Tekt1 and anti-centrosome (ANA) antibodies in mouse testis sections

   PMID:11089920

   Open questions at the time

   • Localization pattern alone does not demonstrate a nucleation function
   • No loss-of-function test of the proposed axoneme-nucleating role in this study
2. 2018 High

   Extended TEKT1 beyond sperm to motile and primary cilia and tied human disease mutations to ciliary motility defects, defining it as a broadly required ciliary protein.

   Evidence Immunolocalization in patient airway and cycling cells, biallelic mutation analysis, zebrafish tekt1 morpholino knockdown with live ciliary-motility imaging, and tekt1/wdr19 genetic epistasis

   PMID:29121203

   Open questions at the time

   • Mechanism of the WDR19/IFT-A genetic interaction not resolved at the molecular level
   • No ultrastructural defect identified despite motility loss
3. 2022 Medium

   Identified a post-transcriptional control circuit, showing TEKT1 levels are tuned by miR-199-5p and that this dosage matters for flagellar assembly.

   Evidence Luciferase reporter validation of direct miR-199-5p/Tekt1 3′UTR targeting plus in vivo antagomir/agomir manipulation in diploid crucian carp

   PMID:35418106

   Open questions at the time

   • Performed in fish model; conservation of regulation in mammals not shown
   • Apoptosis phenotype may be indirect rather than a direct TEKT1 function
4. 2024 Medium

   Provided a physical regulator of TEKT1 localization, showing TBC1D21 binds TEKT1 and controls its proper axonemal deposition during tail formation.

   Evidence Comparative sperm proteomics and reciprocal co-immunoprecipitation in Tbc1d21-null mice, with TEKT1/RAB10 co-localization and ultrastructural analysis

   PMID:38822685

   Open questions at the time

   • Direct vs. indirect nature of the TBC1D21–TEKT1 interaction not dissected by mapping
   • Role of RAB10/transport machinery in TEKT1 delivery inferred from co-localization
5. 2026 High

   Definitively assigned TEKT1 a structural role as a tektin-bundle component required for doublet-microtubule integrity and motility, distinguishing it functionally from paralog TEKT5.

   Evidence Germline Tekt1-knockout mice with fertility and sperm-motility assays, structural analysis of the tektin bundle, phosphoproteomics, and comparison with fertile Tekt5-KO

   PMID:41764189

   Open questions at the time

   • Molecular basis of functional divergence from other tektins not defined
   • How tektin-bundle loss mechanistically impairs motility not fully resolved
6. 2025 Low

   Raised a candidate non-ciliary, cancer-associated function via an AMPK-γ interaction, though this remains the least-substantiated activity.

   Evidence Single co-immunoprecipitation plus proliferation/migration/invasion/apoptosis assays with TEKT1 knockdown/overexpression in endometrial cancer cells

   PMID:39794059

   Open questions at the time

   • Single Co-IP without reciprocal validation or interaction mapping
   • AMPK-γ/ACC/FASN pathway placement not validated by mutagenesis or reconstitution
   • Relationship to the established ciliary/flagellar structural role unclear

• How TEKT1 filaments assemble into and stabilize the tektin bundle within doublet microtubules, and what governs its switch between centrosome/basal-body association and axonemal incorporation, remain unresolved.
• No high-resolution structure of TEKT1 within the assembled tektin bundle reported in the corpus
• Recruitment/handoff mechanism from basal body to axoneme not defined
• Whether the cancer-associated AMPK-γ activity is mechanistically distinct from the structural role is unknown