Title: | TORC1 signaling exerts spatial control over microtubule dynamics by promoting nuclear export of Stu2 |
Author(s): | van der Vaart B; Fischbock J; Mieck C; Pichler P; Mechtler K; Medema RH; Westermann S; |
Address: | "Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria b.vd.vaart@nki.nl. Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam, Netherlands. Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria. Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria stefan.westermann@uni-due.de. Department of Molecular Genetics, Faculty of Biology, Center for Medical Biotechnology, University of Duisburg-Essen, Essen, Germany" |
ISSN/ISBN: | 1540-8140 (Electronic) 0021-9525 (Print) 0021-9525 (Linking) |
Abstract: | "The target of rapamycin complex 1 (TORC1) is a highly conserved multiprotein complex that functions in many cellular processes, including cell growth and cell cycle progression. In this study, we define a novel role for TORC1 as a critical regulator of nuclear microtubule (MT) dynamics in the budding yeast Saccharomyces cerevisiae This activity requires interactions between EB1 and CLIP-170 plus end-tracking protein (+TIP) family members with the TORC1 subunit Kog1/Raptor, which in turn allow the TORC1 proximal kinase Sch9/S6K1 to regulate the MT polymerase Stu2/XMAP215. Sch9-dependent phosphorylation of Stu2 adjacent to a nuclear export signal prevents nuclear accumulation of Stu2 before cells enter mitosis. Mutants impaired in +TIP-TORC1 interactions or Stu2 nuclear export show increased nuclear but not cytoplasmic MT length and display nuclear fusion, spindle positioning, and elongation kinetics defects. Our results reveal key mechanisms by which TORC1 signaling controls Stu2 localization and thereby contributes to proper MT cytoskeletal organization in interphase and mitosis" |
Keywords: | "Active Transport, Cell Nucleus Cell Nucleus/*metabolism Interphase Kinetics Mating Factor/genetics/metabolism Membrane Proteins/genetics/*metabolism Microtubule-Associated Proteins/genetics/*metabolism Microtubules/genetics/*metabolism Mitosis Phosphoryla;" |
Notes: | "Medlinevan der Vaart, Babet Fischbock, Josef Mieck, Christine Pichler, Peter Mechtler, Karl Medema, Rene H Westermann, Stefan eng 2017/10/04 J Cell Biol. 2017 Nov 6; 216(11):3471-3484. doi: 10.1083/jcb.201606080. Epub 2017 Sep 29" |