Genetic and biochemical basis of receptor regulation by ERAS E3 ubiquitin ligases

Research Mentor(s)

Dahlberg, Lina

Description

Proteins are the molecular machinery of the cell. Normally, proteins that are misfolded or do not function properly are marked and targeted for degradation, and accumulation of these misfolded proteins is implicated in several human neurological diseases. Ubiquitin ligases are enzymes that regulate misfolded proteins by marking them for destruction. Cells that are unable to produce ubiquitin ligases show abnormalities in protein regulation which can result in the dangerous build up of misfolded proteins. Transmembrane proteins, including receptors, are processed in the endoplasmic reticulum of the cell before being sent to the membrane. If a receptor has been made or processed incorrectly, it will be targeted by endoplasmic-reticulum-associated degradation (ERAD) and subsequently degraded. Our research focuses on three enzymes that function in the ERAD system in the model organism, Caenorhabditis elegans. C. elegans that harbor a mutation in these three genes, hrd-1, hrdl-1, and marc-6, show differences in protein accumulation. This project focuses on glutamate receptor protein GLR-1, which resides in the membrane of neurons. Glutamate receptors play a major role during learning and memory formation in higher organisms. Here, we show results of reverse-transcriptase (RT)-PCR and EndoH (glycosylase) experiments designed to help determine if and how mutation of E3 ubiquitin ligases may impact protein trafficking and abundance. Our data will help us understand how ERAD regulates GLR-1 processing via two E3 ubiqutin ligases, marc-6 and hrdl-1.

Document Type

Event

Start Date

17-5-2017 12:00 PM

End Date

17-5-2017 3:00 PM

Department

Biology

Genre/Form

student projects; posters

Subjects – Topical (LCSH)

Glutamine--Receptors; Ligases; Ubiquitin; Nervous system--Degeneration--Pathophysiology

Type

Image

Rights

Copying of this document in whole or in part is allowable only for scholarly purposes. It is understood, however, that any copying or publication of this documentation for commercial purposes, or for financial gain, shall not be allowed without the author's written permission.

Language

English

Format

application/pdf

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May 17th, 12:00 PM May 17th, 3:00 PM

Genetic and biochemical basis of receptor regulation by ERAS E3 ubiquitin ligases

Proteins are the molecular machinery of the cell. Normally, proteins that are misfolded or do not function properly are marked and targeted for degradation, and accumulation of these misfolded proteins is implicated in several human neurological diseases. Ubiquitin ligases are enzymes that regulate misfolded proteins by marking them for destruction. Cells that are unable to produce ubiquitin ligases show abnormalities in protein regulation which can result in the dangerous build up of misfolded proteins. Transmembrane proteins, including receptors, are processed in the endoplasmic reticulum of the cell before being sent to the membrane. If a receptor has been made or processed incorrectly, it will be targeted by endoplasmic-reticulum-associated degradation (ERAD) and subsequently degraded. Our research focuses on three enzymes that function in the ERAD system in the model organism, Caenorhabditis elegans. C. elegans that harbor a mutation in these three genes, hrd-1, hrdl-1, and marc-6, show differences in protein accumulation. This project focuses on glutamate receptor protein GLR-1, which resides in the membrane of neurons. Glutamate receptors play a major role during learning and memory formation in higher organisms. Here, we show results of reverse-transcriptase (RT)-PCR and EndoH (glycosylase) experiments designed to help determine if and how mutation of E3 ubiquitin ligases may impact protein trafficking and abundance. Our data will help us understand how ERAD regulates GLR-1 processing via two E3 ubiqutin ligases, marc-6 and hrdl-1.