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Ego3, a regulator of TORC1 signaling, is degraded by the intralumenal fragment pathway


Ego3, a regulator of TORC1 signaling, is degraded by the intralumenal fragment pathway

Jin, Qiao (2018) Ego3, a regulator of TORC1 signaling, is degraded by the intralumenal fragment pathway. Masters thesis, Concordia University.

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Jin_MSc_F2018.pdf - Accepted Version
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Target of rapamycin complex 1 (TORC1) is a conserved protein kinase complex whose activity controls metabolism in eukaryotic cells. To function, TORC1 and its regulators are localized to lysosome membranes. The mechanism(s) that control TOR complex protein lifetimes remain enigmatic. The IntraLumenal Fragment (ILF) pathway is a selective protein degradation pathway that involves lysosomes. Thus, I hypothesized that components of TORC1, EGO and SEA complexes may be degraded by this ILF pathway.
Using the yeast S. cerevisiae and its vacuolar lysosome (or vacuole) as models, I tested this hypothesis by first imaging live cells by fluorescence microscopy. I found that several subunits of TORC1, EGO and SEA complexes tagged with GFP are sorted into boundaries between docked vacuoles and accumulate within the vacuole lumen. However, when I isolated vacuoles from cells and repeated this experiment in vitro, I found that nearly all components re-localized to endosomes. The only exception was Ego3, a subunit that tethers the EGO complex to vacuole membranes. I then applied rapamycin, an inhibitor of TOR, to induce TOR protein downregulation and degradation. In vivo, I found that rapamycin stimulated sorting of TOR complex . Whereas, in vitro, rapamycin only enhanced sorting, internalization and degradation of Ego3.
In conclusion, many components of TOR signaling complexes seem to be degraded by the ILF pathway including Ego3. Thus, I speculate that the ILF pathway may play an important role in downregulating TOR activity.

Divisions:Concordia University > Faculty of Arts and Science > Biology
Item Type:Thesis (Masters)
Authors:Jin, Qiao
Institution:Concordia University
Degree Name:M.A. Sc.
Date:July 2018
Thesis Supervisor(s):Brett, Christopher and Titorenko, Vladimir and Piekny, Alisa and Darlington, Peter
ID Code:984199
Deposited By: Qiao Jin
Deposited On:16 Nov 2018 16:32
Last Modified:16 Nov 2018 16:32
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