Date of Award

5-2022

Document Type

Thesis campus only

Department

Biology

First Advisor

Bethany Strunk

Second Advisor

Kelly Lyons

Third Advisor

Luis Giavedoni

Abstract

The goal of this study is to identify and investigate a candidate protein partner mediating complex independent Fig4 functions in yeast cells. The results presented here begin with the discovery that Fig4 disease related mutants in yeast: 1) bind poorly to Vac14 and, therefore, the Fab1-Vac14-Fig4 complex thereby failing to influence both the synthesis and turnover of PI3,5P2; and 2) these same mutants exhibit elevated growth rates when exposed to rapamycin, a growth inhibitor that potently inhibits TORC1 signaling, and mild heat stress. The data presented here suggests that this growth advantage is related to non-catalytic functions of Fig4 that occur when separated from its known protein complex. Additionally, the data indicates that this novel function is likely mediated or directly involves Ste20 under certain stress conditions. Discovering the physiological role of the relationship between Ste20, TORC1 signaling, and Fig4 in response to specific stresses stands to expand our area of inquiry into demyelinating diseases in humans.

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