Date Approved
2019
Degree Type
Open Access Thesis
Degree Name
Master of Science (MS)
Department or School
Chemistry
Committee Member
Hedeel Evans, PhD
Committee Member
Deborah Heyl-Clegg, PhD
Committee Member
Jeffery Guthrie, PhD
Abstract
Dopamine receptors D1R and D2R form a heterooligomeric complex with signaling properties distinct from the individual receptors. Aberrant expression of this protein-protein complex is linked to the etiology of various neuropsychiatric diseases. Formation of the D1R-D2R heteromer is thought to be dependent upon electrostatic interactions occurring between the carboxyl tail of D1R and the third intracellular loop of D2R. Using this interaction site as template, I synthesized several peptides designed to disrupt the minimal area of the D1R-D2R interaction interface and tested these using whole cell lysates of human brain tissue and dopamine receptor constructs. I report that a synthetic peptide with the sequence EAARRAQE is efficient in blocking D1R-D2R interaction, while shorter and more highly charged peptides (EERRAQ, ARRA and AARRAQ) had no effect. This research provides insight into the binding regions involved in D1-D2 heteromer formation, and may aid future drug development efforts that target this receptor complex.
Recommended Citation
Champion, Margaret M., "Unravelling the D1R-D2R heteromer" (2019). Master's Theses and Doctoral Dissertations. 988.
https://commons.emich.edu/theses/988
