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Permanent link (DOI): https://doi.org/10.7939/R3QD3N

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The Herp and HRD1-dependent degradation of TRPP2 Open Access

Descriptions

Other title
Subject/Keyword
calcium signaling
endoplasmic reticulum stress
polycystic kidney disease
Herp
HRD1
TRPP2
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
Lara, Carlos J.
Supervisor and department
Chen, Xing-Zhen (Physiology)
Examining committee member and department
Casey, Joseph (Biochemistry)
Ho, Anthony (Physiology)
Cordat, Emmanuelle (Physiology)
Department
Department of Physiology
Specialization

Date accepted
2012-09-24T13:28:40Z
Graduation date
2012-09
Degree
Master of Science
Degree level
Master's
Abstract
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a prevalent genetic disorder where multiple fluid-filled cysts destroy kidney architecture, eventually requiring hemodialysis or kidney transplant. Approximately 15% of cases of ADPKD cases are caused by defects in TRPP2, a calcium permeable, non-selective cation channel protein in the ER and plasma membrane. Studies by our lab indicate that TRPP2 immunoprecipitates with ER stress-regulated proteins Herp and HRD1. Herp is an endoplasmic reticulum (ER) integral membrane protein involved in the ubiquitylation and degradation of substrates by ER associated degradation (ERAD). HRD1 functions as an E3 ubiquitin ligase and is important in retrotranslocation of ERAD substrates. This study sought to examine the interaction between TRPP2 and Herp/HRD1. Our findings suggest that Herp cleavage affects its TRPP2 binding affinity, but not ubiquitylation. We also confirmed that HRD1 interacts with TRPP2, and may be involved in its ubiquitylation.
Language
English
DOI
doi:10.7939/R3QD3N
Rights
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
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File size: 7833756
Last modified: 2015:10:12 11:50:10-06:00
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File title: Thesis Title
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File author: Carlos Lara
Page count: 135
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