Abstract
Microtubule-organizing centers recruit α- and β-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.
Highlights
Understanding how the centrosomal components function and are organized during the cell cycle could shed light on many human diseases, from ciliary syndromes to cancer
We observed one tubulin cofactor D (TBCD) spot accompanying the primary cilium in cells at G1, which we identified as occurring at the daughter centriole by double immunostaining with an antibody that recognizes e-tubulin, which did not co-localize with TBCD (Figure 1B–D)
We have shown that TBCD is concentrated at the centrioles and basal bodies, where it plays roles in centriologenesis, ciliogenesis, and spindle organization
Summary
Understanding how the centrosomal components function and are organized during the cell cycle could shed light on many human diseases, from ciliary syndromes to cancer. Centrioles, which are required to assemble the axonemes of cilia and flagella, are structurally very complex In mammals, they are 500 nm long cylinders with a 200 nm diameter consisting of nine blades arranged in a circle, each containing three highly specialized microtubule segments. One of the most widely accepted concepts is that MTOCs, and in particular the centrosome, accumulate ab-tubulin polypeptides as part of the PCM for microtubule nucleation This suggests that there is some tubulin supply at the MTOCs. Yet, the assembly of ab-tubulin heterodimers is not a trivial matter. Human TBCD (HsTBCD) has been shown to play a role in the organization of the mitotic spindle, and has been hypothesized to recruit from among cytosolic centrosomal proteins, such as pericentrin or c-tubulin [24]
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