Tim Stearns, Stanford University, Centrosomes, cilia, and cell polarity

Tubulins are a conserved superfamily of proteins that are important in the structure and function of the microtubule cytoskeleton. We have characterized in vertebrates the final member of the tubulin superfamily, zeta-tubulin. In multiciliated cells, zeta-tubulin is a component of the basal foot, a centriolar appendage that connects centrioles to the apical cytoskeleton. Depletion of zeta-tubulin results in disorganization of basal body distribution and polarity in multiciliated cells, but no apparent phenotypes in other cell types. In contrast with multiciliated cells, zeta-tubulin in cycling cells does not localize to centrioles and instead is associated with the TRiC-CCT complex, a large cytoplasmic chaperone that is responsible for folding actin, tubulin, and other proteins. We conclude that zeta-tubulin enables the basal bodies of differentiated cells to orient with respect to the cell and tissue axes. Our results suggest that zeta-tubulin function is shared with delta- and epsilon-tubulins, and thus has brought us closer to understanding the function of the tubulin superfamily as a whole. Finally, Zeta-tubulin is the first protein described to be regulated at the level of folding in a cell-type specific manner.