Degree
Master of Science
Program
Physiology and Pharmacology
Supervisor
Dr. Stephen Ferguson
Abstract
β-arrestins are versatile adaptor proteins that play a vital role in regulation of G protein coupled receptor (GPCR) trafficking and signalling properties. PDZ proteins have previously been shown to modulate β-arrestin2 recruitment and receptor internalization for many GPCRs including Corticotropin-Releasing Factor Receptor 1 (CRFR1), a receptor whose antagonists have been shown to demonstrate both anxiolytic- and antidepressant-like effects. Further characterization of the interplay between β-arrestins and PDZ proteins may aid in determining a potential mechanism for PDZ protein regulation of GPCR trafficking. Our findings suggest that PDZ proteins PSD-95, MAGI1, and PDZK1 complex with β-arrestin2 by interacting via the PDZ domain. Using a proteomic approach, mutational analyses were used to reveal that the β-arrestin2 A175F mutant impairs interaction with PSD-95. Additionally, this mutant form of β-arrestin2 shows decreased CRF-stimulated recruitment to CRFR1. Thus, investigating how β-arrestins and PDZ proteins interact could provide further insight into GPCR trafficking properties and the development of novel therapeutics.
Recommended Citation
Gupta, Sarah, "PDZ Protein Regulation of β-arrestin Recruitment and GPCR Trafficking" (2016). Electronic Thesis and Dissertation Repository. 4374.
https://ir.lib.uwo.ca/etd/4374