TY - JOUR
T1 - TOR signaling regulates microtubule structure and function
AU - Choi, Jae H.
AU - Adames, Neil R.
AU - Chan, Ting Fung
AU - Zeng, Chenbo
AU - Cooper, John A.
AU - Zheng, X. F.Steven
N1 - Funding Information:
We thank D. Dean for reading this manuscript, G. Fink, D. Pellman, C. Hardy, P. James and A. Straight for strains, plasmids and libraries, A. Chan for mAb 9E10, and M. Walter and D. Dean for assistance with and use of their microscopy facilities. This work was supported by grants from NIH (J.A.C. and X.F.Z), a HHMI New Investigator Award and a startup fund from Washington University (X.S.Z.). X.S.Z. was a Coleman Foundation Scholar.
PY - 2000/7/1
Y1 - 2000/7/1
N2 - 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 bikΔ mutant. Our data suggest a role for TOR signaling in regulating microtubule stability and function, possibly through Bik1p.
AB - 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 bikΔ mutant. Our data suggest a role for TOR signaling in regulating microtubule stability and function, possibly through Bik1p.
UR - http://www.scopus.com/inward/record.url?scp=0034644122&partnerID=8YFLogxK
U2 - 10.1016/S0960-9822(00)00599-6
DO - 10.1016/S0960-9822(00)00599-6
M3 - Article
C2 - 10899009
AN - SCOPUS:0034644122
SN - 0960-9822
VL - 10
SP - 861
EP - 864
JO - Current Biology
JF - Current Biology
IS - 14
ER -