TOR signaling regulates microtubule structure and function

The functional diversity and structural heterogeneity of microtubules are l argely determined by microtubule associated proteins (MAPs) [1,2], Bik1p (b ilateral karyogamy defect protein) Is one of the MAPs required for microtub ule assembly, stability and function in cell processes such as karyogamy an d nuclear migration and positioning in the yeast Saccharomyces cerevisiae [ 3], The macrocyclic immunosuppressive antibiotic rapamycin, complexed with its binding protein FKBP12, binds to and inhibits the target of rapamycin p rotein (TOR) in yeast [4,5]. We report here that TOR physically interacts w ith Bik1p, the yeast homolog of human CLIP-170/Restin [6,7]. Inhibition of TOR by rapamycin significantly affects microtubule assembly, elongation and stability. This function of TOR is independent of new protein synthesis. R apamycin also causes defects in spindle orientation, nuclear movement and p ositioning, karyogamy and chromosomal stability, defects also found in the bik Delta mutant. Our data suggest a role for TOR signaling in regulating m icrotubule stability and function, possibly through Bik1p.