title: TOR signaling regulates microtubule structure and function.
abstract: The functional diversity and structural heterogeneity of microtubules are largely determined by microtubule-associated proteins (MAPs) [1] [2]. Bik1p (bilateral karyogamy defect protein) is one of the MAPs required for microtubule assembly, stability and function in cell processes such as karyogamy and 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 protein (TOR) in yeast [4] [5]. We report here that TOR physically interacts with 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. Rapamycin also causes defects in spindle orientation, nuclear movement and positioning, karyogamy and chromosomal stability, defects also found in the bikDelta mutant. Our data suggest a role for TOR signaling in regulating microtubule stability and function, possibly through Bik1p.
authors.affiliation: Departments of Pathology, Washington University School of Medicine, St Louis, MO 63110, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Choi
authors.forename: N R
authors.initials: NR
authors.lastname: Adames
authors.forename: T F
authors.initials: TF
authors.lastname: Chan
authors.forename: C
authors.initials: C
authors.lastname: Zeng
authors.forename: J A
authors.initials: JA
authors.lastname: Cooper
authors.forename: X F
authors.initials: XF
authors.lastname: Zheng
mesh_terms: D005656:Fungal Proteins / Q000502:physiology*; D006801:Humans; D008870:Microtubules / Q000187:drug effects / Q000502:physiology*; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D008941:Spindle Apparatus / Q000187:drug effects
chemical_list: D005656:Fungal Proteins; D020123:Sirolimus