Type

Text

Type

Dissertation

Advisor

Scarlata, Suzanne | Nicole Sampson | Mario Rebecchi | London, Erwin | David F. Green.

Date

2010-12-01

Keywords

Biophysics _ Cellular Biology | Cell Biology, FRET, G protein, Phospholipase C, RNA

Department

Department of Biochemistry and Structural Biology

Language

en_US

Source

This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree.

Identifier

http://hdl.handle.net/11401/70925

Publisher

The Graduate School, Stony Brook University: Stony Brook, NY.

Format

application/pdf

Abstract

Mammalian inositol-specific phospholipase Cβ1 (PLCβ1) is activated by Gαq subunits on the plasma membrane where it catalyzes hydrolysis of the minor membrane phosphatidylinositol 4,5 bisphosphate. While PLCβ1 localizes primarily to the plasma membrane it also exists in other compartments of the cell. It is not currently known what function PLCβ1 has in the cytosol and nucleus nor is it known what factors localize PLCβ1 to these compartments. In this study, we have identified a novel binding partner, translin-associated factor X (TRAX). Our experiments show that both proteins interact in solution and in cells. While TRAX exerts little effect on the membrane binding of PLCβ1, it does reduce the affinity of PLCβ1 for Gαq and inhibits the stimulation of PLCβ1 activity by Gαq. TRAX, a cytosolic protein that can localize to the nucleus, isinvolved in the down-regulation of protein expression by RNA interference. Our study shows that cytosolic PLCβ1 can drive TRAX out of the nucleus and reduce siRNA activity. Furthermore, activation of Gαq results in apparent displacement of cytosolic PLCβ1 from TRAX and concurrently allows TRAX to relocalize to the nucleus. Importantly we have found that increased cytosolic expression of PLCβ1 appears to reverse the siRNA-induced down-regulation of GAPDH. Our data suggests a potential link between Gαq activation, PLCβ1 localization and siRNA activity.

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.