Research Mentor(s)

Dahlberg, Lina

Description

Endoplasmic reticulum-associated degradation (ERAD) maintains cellular health by removing misfolded proteins from the endoplasmic reticulum (ER). ERAD is ubiquitin-dependent, and ubiquitination of target proteins can be catalyzed by ER-resident E3 ubiquitin ligases. In C. elegans, genes for three putative ERAD E3 ubiquitin ligases have been identified: hrd-1, hrdl-1, and marc-6 (HRD-1, GP78/AMFR, and MARCH-6 in mammalian systems). In C. elegans, these three genes cooperate to maintain the overall health of animals during ER stress. We are testing the roles of hrd-1, hrdl-1, and marc-6 in the neurons of C. elegans. GLR-1 is a glutamate receptor that is expressed in a subset of interneurons in C. elegans. It is homologous to human AMPA-type glutamate receptors, which are central for the processes of learning and memory. GLR-1 that is tagged with GFP (GLR-1::GFP) recapitulates normal biochemical GLR-1 function and allows observation of its abundance and localization in live animals. Animals harboring mutations in the ERAD E3 ligases hrd-1 and hrdl-1 have increased GLR-1::GFP abundance compared to wild-type animals. hrd-1 and hrdl-1 mutants also show defects in GLR-1::GFP localization. Double mutant analysis suggests that hrdl-1 and hrd-1 do not act redundantly, but could act in the same pathway. We are currently testing how a mutation in marc-6 affects GLR-1::GFP. Future experiments will focus on determining the mechanism(s) by which GLR-1 is selected as a substrate by the ERAD E3 ligases and their associated E2 ligases.

Document Type

Event

Start Date

19-5-2016 12:00 PM

End Date

19-5-2016 3:00 PM

Department

Biology

Genre/Form

student projects; posters

Subjects – Topical (LCSH)

Caenorhabditis elegans--Genetics; Cell receptors

Type

Image

Keywords

Biology, molecular biology, model organism, C. elegans, glutamate, receptor, protein, mutant, genetics, ubiquitin, endoplasmic reticulum, GLR-1

Comments

Outstanding Poster Award Recipient

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

Included in

Biology Commons

Share

COinS
 
May 19th, 12:00 PM May 19th, 3:00 PM

Regulation of AMPA-type glutamate receptor homolog GLR-1 by ERAD ubiquitin ligases in C. elegans

Endoplasmic reticulum-associated degradation (ERAD) maintains cellular health by removing misfolded proteins from the endoplasmic reticulum (ER). ERAD is ubiquitin-dependent, and ubiquitination of target proteins can be catalyzed by ER-resident E3 ubiquitin ligases. In C. elegans, genes for three putative ERAD E3 ubiquitin ligases have been identified: hrd-1, hrdl-1, and marc-6 (HRD-1, GP78/AMFR, and MARCH-6 in mammalian systems). In C. elegans, these three genes cooperate to maintain the overall health of animals during ER stress. We are testing the roles of hrd-1, hrdl-1, and marc-6 in the neurons of C. elegans. GLR-1 is a glutamate receptor that is expressed in a subset of interneurons in C. elegans. It is homologous to human AMPA-type glutamate receptors, which are central for the processes of learning and memory. GLR-1 that is tagged with GFP (GLR-1::GFP) recapitulates normal biochemical GLR-1 function and allows observation of its abundance and localization in live animals. Animals harboring mutations in the ERAD E3 ligases hrd-1 and hrdl-1 have increased GLR-1::GFP abundance compared to wild-type animals. hrd-1 and hrdl-1 mutants also show defects in GLR-1::GFP localization. Double mutant analysis suggests that hrdl-1 and hrd-1 do not act redundantly, but could act in the same pathway. We are currently testing how a mutation in marc-6 affects GLR-1::GFP. Future experiments will focus on determining the mechanism(s) by which GLR-1 is selected as a substrate by the ERAD E3 ligases and their associated E2 ligases.

 

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.