Review: Postchaperonin tubulin folding cofactors and their role in microtubule dynamics

The microtubule cytoskeleton consists of a highly organized network of micr otubule polymers bound to their accessory proteins: microtubule-associated proteins, molecular motors, and microtubule-organizing proteins. The microt ubule subunits are heterodimers composed of one alpha -tubulin polypeptide and one beta -tubulin polypeptide that should undergo a complex folding pro cessing before they achieve a quaternary structure that will allow their in corporation into the polymer. Due to the extremely high protein concentrati on that exists at the cell cytoplasm, there are alpha- and beta -tubulin in teracting proteins that prevent the unwanted interaction of these polypepti des with the surrounding protein pool during folding, thus allowing microtu bule dynamics. Several years ago, the development of a nondenaturing electr ophoretic technique made it possible to identify different tubulin intermed iate complexes during tubulin biogenesis in vitro. By these means, the cyto solic chaperonin containing TCP-1 (CCT or TriC) and prefoldin have been dem onstrated to intervene through tubulin and actin folding. Various other cof actors also identified along the alpha- and beta -tubulin postchaperonin fo lding route are now known to have additional roles in tubulin biogenesis su ch as participating in the synthesis, transport, and storage of alpha- and beta -tubulin. The future characterization of the tubulin-binding sites to these proteins, and perhaps other still unknown proteins, will help in the development of chemicals that could interfere with tubulin folding and thus modulating microtubule dynamics. In this paper, current knowledge of the a bove postchaperonin folding cofactors, which are in fact chaperones involve d in tubulin heterodimer quaternary structure achievement, will be reviewed . (C) 2001 Academic Press.