Protection from Free  -Tubulin by the  -Tubulin Binding Protein Rbl2p

Free beta-tubulin not in heterodimers with alpha-tubulin can be toxic, disrupting microtubule assembly and function. We are interested in the mechanisms by which cells protect themselves from free beta-tubulin. This study focused specifically on the function of Rb12p, which, like alpha-tubulin, can rescue cells from free beta-tubulin. In vitro studies of the mammalian homolog of Rb12p, cofactor A, have suggested that Rb12p/cofactor A may be involved in tubulin folding. Here we show that Rb12p becomes essential in cells containing a modest excess of beta-tubulin relative to alpha-tubulin. However, this essential activity of Rb12p/cofactor A does not depend upon the reactions described by the in vitro assay. Rescue of beta-tubulin toxicity requires a minimal but substoichiometric ratio of Rb12p to beta-tubulin. The data suggest that Rb12p binds transiently to free beta-tubulin, which then passes into an aggregated form that is not toxic.