TBCD links centriologenesis, spindle microtubule dynamics, and midbody abscission in human cells.
Microtubule-organizing centers recruit alpha- and beta-tubulin polypeptides for microtubule nucleation. Tubulin synthesis is complex, requiring five specific cofactors, designated tubulin cofactors (TBCs) A-E, which contribute to various aspects of microtubule dynamics in vivo. Here, we show that tubulin cofactor D (TBCD) is concentrated at the centrosome and midbody, where it participates in centriologenesis, spindle organization, and cell abscission. TBCD exhibits a cell-cycle-specific pattern, localizing on the daughter centriole at G1 and on procentrioles by S, and disappearing from older centrioles at telophase as the protein is recruited to the midbody. Our data show that TBCD overexpression results in microtubule release from the centrosome and G1 arrest, whereas its depletion produces mitotic aberrations and incomplete microtubule retraction at the midbody during cytokinesis. TBCD is recruited to the centriole replication site at the onset of the centrosome duplication cycle. A role in centriologenesis is further supported in differentiating ciliated cells, where TBCD is organized into "centriolar rosettes". These data suggest that TBCD participates in both canonical and de novo centriolar assembly pathways.
Fanarraga
Mónica López
ML
Departamentos de Biología Molecular, Instituto de Formación e Investigación Marqués de Valdecilla Facultad de Medicina, Universidad de Cantabria, Santander, Spain.
Bellido
Javier
J
Jaén
Cristina
C
Villegas
Juan Carlos
JC
Zabala
Juan Carlos
JC
D000818:Animals; D002453:Cell Cycle; D002502:Centrioles; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D018613:Microscopy, Confocal; D008869:Microtubule-Associated Proteins / Q000502:physiology*; D034622:RNA Interference; D008941:Spindle Apparatus
D008869:Microtubule-Associated Proteins