In vitro reconstitution of Slm1 mediated TORC2 activation

Diplôme Thèse In vitro reconstitution of Slm1 mediated TORC2 activation eng 2018-02-16 author Vegunta Yogesh 794828 director Loewith Robbie Joséph 630703 director Vadas Oscar 0000-0003-3511-6479 508966 10.13097/archive-ouverte/unige:107261 urn:nbn:ch:unige-1072611 Sc. 5179 Growth is a fundamental property of cells and is regulated in response to nutritional/environmental conditions a cell is experiencing. This regulation comes from signaling pathways that cells possess. TOR, an essential eukaryotic kinase, through TORC1 and TORC2 regulates cellular/organismal growth homeostasis. In S. cerevisiae, TORC2 is anchored at plasma membrane in MCTs. Increase in PM tension causes Slm1 to relocate from eisosomes to MCTs to activate TORC2. However, mechanism of how Slm1 activate TORC2 remains unknown. We identified that Slm1 BAR and PH domains are sufficient to perform its functions. We show that Slm1 BAR domain contributes to PI(4,5)P2 binding indirectly through dimerization which brings two PI(4,5)P2 binding PH domains in close vicinity. We showed that Slm1 oligomerizes via it's BAR domain that remodels membranes. We show that oligomerization together with PI(4,5)P2 binding are essential for Slm1 to activate TORC2. We provide a biochemical reconstitution of Slm1 mediated TORC2 activation. Cell growth Cell surface area regulation Membrane tension Protein and Lipid Dewey 570 Dewey 615 43 Département de biologie moléculaire 161 31 Section des sciences pharmaceutiques 17 false 56a43e4c-46cc-4e72-ba27-c41537a79e24 Thesis Restricted YV_Thesis_final-number.pdf 5574927 application/pdf Private 2019-02-27 2fbb854116dec6310437cc8d10702fbda0f2a1d13104150b5e1c89b82dbb01df restrictedAccess Faculté des sciences / Section de biologie / Département de biologie moléculaire Faculté des sciences / Section des sciences pharmaceutiques

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In vitro reconstitution of Slm1 mediated TORC2 activation				2018	786	13

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Vegunta, Yogesh