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Abstract
Free β-tubulin not in heterodimers with α-tubulin can be toxic, disrupting microtubule assembly and function. We are interested in the mechanisms by which cells protect themselves from free β-tubulin. This study focused specifically on the function of Rbl2p, which, like α-tubulin, can rescue cells from free β-tubulin. In vitro studies of the mammalian homolog of Rbl2p, cofactor A, have suggested that Rbl2p/cofactor A may be involved in tubulin folding. Here we show that Rbl2p becomes essential in cells containing a modest excess of β-tubulin relative to α-tubulin. However, this essential activity of Rbl2p/cofactorA does not depend upon the reactions described by the in vitro assay. Rescue of β-tubulin toxicity requires a minimal but substoichiometric ratio of Rbl2p to β-tubulin. The data suggest that Rbl2p binds transiently to free β-tubulin, which then passes into an aggregated form that is not toxic.
We thank R. Himes and M. Gupta at the University of Kansas for the gift of purified yeast tubulin. We thank the Philippsen (Universität Basel, Basel, Switzerland), Young (Massachusetts Institute of Technology [MIT]), and Fink (MIT) laboratories for plasmids. We thank A. Rushforth and other members of our laboratory, members of MIT M&M, A. Grossman (MIT), S. Bell (MIT), and S. Sanders (MIT) for valuable discussions.
K.C.A. and A.S. were supported in part by a training grant from the National Institute of General Medical Sciences to the Department of Biology, MIT. W.C. was supported in part by an HHMI Undergraduate Biological Sciences Education Program grant to the Department of Biology, MIT. This work was supported by a grant to F.S. from the National Institute of General Medical Sciences.