TUBE1

TUBE1 (tubulin epsilon chain / delta-tubulin) is a centriole-associated tubulin family member that functions within a conserved tetrameric complex together with epsilon-tubulin, TEDC1, and TEDC2 to build and maintain centriole triplet microtubules, thereby enabling centriole maturation and inheritance across cell cycles (PMID:28906251, PMID:40067174). TUBE1 localizes to centrioles independently of cytoplasmic microtubules and is distinct in its distribution from gamma-tubulin and epsilon-tubulin within the centrosome (PMID:10620804). Loss of TUBE1 abolishes triplet microtubule formation, prevents recruitment of the central core protein POC5, and causes a futile cycle in which centrioles form but disintegrate each cell division — a phenotype suppressible by paclitaxel-mediated microtubule stabilization (PMID:28906251).

1. 2000 Medium

   Establishing TUBE1 as a centriolar protein resolved its subcellular context: unlike gamma-tubulin, TUBE1 localizes to centrioles themselves rather than pericentriolar material, and it does so independently of microtubules, raising the question of what structural role it plays there.

   Evidence Immunofluorescence with microtubule-depolymerization controls in human cells

   PMID:10620804

   Open questions at the time

   • Single-lab observation without independent replication at this time
   • No functional perturbation to determine whether TUBE1 is required for centriole structure or duplication
   • Molecular partners at the centriole were unidentified
2. 2017 High

   Loss-of-function analysis revealed that TUBE1 is essential for triplet microtubule formation: without it, centrioles lack triplets, fail to recruit the central core protein POC5, cannot mature, and undergo disintegration each cell cycle — establishing TUBE1 as a structural determinant of centriole integrity and inheritance.

   Evidence CRISPR knockout in human cells with electron microscopy ultrastructure, co-immunoprecipitation showing delta–epsilon tubulin interaction, and paclitaxel rescue of centriole stability

   PMID:28906251

   Open questions at the time

   • Whether TUBE1 acts as part of a larger complex beyond its interaction with epsilon-tubulin was unknown
   • Mechanism by which TUBE1 promotes triplet microtubule nucleation or stabilization was unresolved
   • No structural model of the TUBE1–epsilon-tubulin assembly
3. 2025 High

   Identification of the TUBE1–epsilon-tubulin–TEDC1–TEDC2 tetramer defined the minimal functional unit: all four subunits are mutually required for centrosomal targeting and triplet microtubule formation, and loss of any component phenocopies TUBE1 deletion, establishing the complex as an obligate module for centriole architecture.

   Evidence CRISPR knockout of TEDC1/TEDC2 in human cells, ultrastructure expansion microscopy, reciprocal co-immunoprecipitation, and AlphaFold Multimer structural modeling

   PMID:40067174

   Open questions at the time

   • Biochemical reconstitution of the tetramer and direct demonstration of microtubule-modifying activity in vitro have not been performed
   • How the tetramer is specifically recruited to the centriole proximal end is unknown
   • Whether the tetramer directly nucleates the C-tubule or stabilizes pre-existing doublets remains unresolved

• The direct biochemical mechanism by which the TUBE1-containing tetramer promotes triplet microtubule formation — whether through nucleation, stabilization, or templating of the C-tubule — remains the central open question.
• No in vitro reconstitution of triplet microtubule formation with purified tetramer
• Atomic-resolution experimental structure of the tetramer is lacking
• Relationship between tetramer stoichiometry at the centriole and triplet microtubule number is undefined