Faculty Advisor

Carrisa Olsen

Faculty Advisor

Arne Gericke

Faculty Advisor

Suzanne Scarlata

Identifier

etd-120417-214025

Abstract

"When cells are exposed to environmental stress, they respond by compartmentalizing mRNA and translation proteins in stress granulates to protect mRNA. However, the mechanism through which external stress is communicated into the cell to form stress granules is unknown. Phospholipase Cβ (PLCβ) is activated by Gq on the plasma membrane in response to sensory stimuli to initiate calcium signals resulting in a variety of cellular responses. Here, we show that PLCβ binds to major proteins that organize stress granules as well as the main component of the RNA-induced silencing machinery, Argonaute-2 (Ago2). Under stress, PLCβ moves from the plasma membrane to the cytosol to escort Ago2 into stress granules and potentially inhibit mRNA degradation by regulating microRNAs (miRs) expression. Using a model muscle cell line functionally adapted to handle stress, we find that upon osmotic stress, the movement of PLCβ into the cytosol to move Ago2 into stress granules changes the population and distribution of miRs, and in particular, members of the let family. The impact of changes in let is to acutely affect glucose metabolism allowing cells to adapt to stress conditions. Our studies present a model in which PLCβ relays information about external stress to promote stress granule formation and protect mRNAs."

Publisher

Worcester Polytechnic Institute

Degree Name

MS

Department

Chemistry & Biochemistry

Project Type

Thesis

Date Accepted

2017-12-04

Accessibility

Restricted-WPI community only

Subjects

Phospholipase Cβ, Ago2, stress granules, fluorescence microscopy, osmotic stress

Available for download on Friday, December 04, 2020

Share

COinS