TORC1 signaling exerts spatial control over microtubule dynamics by promoting nuclear export of Stu2

van der Vaart, Babet ORCID; Fischböck, Josef; Mieck, Christine GND; Pichler, Peter ORCID; Mechtler, Karl ORCID; Medema, René H. ORCID; Westermann, Stefan GND

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.

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van der Vaart, B., Fischböck, J., Mieck, C., Pichler, P., Mechtler, K., Medema, R.H., Westermann, S., n.d. TORC1 signaling exerts spatial control over microtubule dynamics by promoting nuclear export of Stu2. https://doi.org/10.1083/jcb.201606080
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