Tubulin folding cofactor D is a microtubule destabilizing protein

A rapid switch between growth and shrinkage at microtubule ends is fundamen tal for many cellular processes. The main structural components of microtub ules, the alpha beta-tubulin heterodimers, are generated through a complex folding process where GTP hydrolysis [Fontalba et al, (1993) J, Cell Sci, 1 06, 627-632] and a series of molecular chaperones are required [Sternlicht et al, (1993) Proc. Natl, Acad, Sci, USA 90, 9422-9426; Campo et al, (1994) FEES Lett. 353, 162-166; Lewis et al, (1996) J, Cell Biol, 132, 1-4; Le,vi s et al, (1997) Trends Cell Biol, 7, 4791184; Tian et al, (1997) J, Cell Bi ol, 138, 821-823], Although the participation of the cofactor proteins alon g the tubulin folding route has been well established in vitro, there is al so evidence that these protein cofactors might contribute to diverse microt ubule processes in vivo [Schwahn ct al, (1998) Nature Genet, 19, 327-332; H irata et al, (1998) EMBO J, 17, 658-666; Fanarraga et al, (1999) Cell Motil , Cytoskel, 43, 243-254], Microtubule dynamics, crucial during mitosis, cel lular motility and intracellular transport processes, are known to be regul ated by at least four known microtubule-destabilizing proteins. OP18/Stathm in and XRCM1 are microtubule catastrophe-inducing factors operating through different mechanisms [Waters and Salmon (1996) Curr, Biol, 6, 361-363; McN ally (1999) Curr, Biol, 9, R274-R276]. Here we show that the tubulin foldin g cofactor D, although it does not co-polymerize with microtubules either i n vivo or in vitro, modulates microtubule dynamics by sequestering beta-tub ulin from GTP-bound alpha beta-heterodimers, (C) 2000 Federation of Europea n Biochemical Societies.