The Herp and HRD1-dependent degradation of TRPP2

• Author / Creator

  Lara, Carlos J.

• 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.

• Subjects / Keywords

  • Herp
  • Polycystic kidney disease
  • Calcium signaling
  • HRD1
  • Endoplasmic reticulum stress
  • TRPP2

• Graduation date

  Fall 2012

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/R3QD3N

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.