DOI
https://doi.org/10.25772/F9D2-FJ74
Author ORCID Identifier
0000-0002-7972-2940
Defense Date
2021
Document Type
Thesis
Degree Name
Master of Science
Department
Physiology and Biophysics
First Advisor
Dr. Javier González Maeso
Second Advisor
Dr. Ian Ramsey
Third Advisor
Dr. Montserrat Samso
Abstract
While the etiology is unknown, serotonin and glutamate G protein-coupled receptors (GPCR) neurotransmission dysfunctionality is characteristic of schizophrenia. Previous findings demonstrated that the serotonin 5-hydroxytryptamine 2A (5-HT2A) receptor and the metabotropic glutamate 2 (mGlu2) receptor assemble into a heteromeric complex; however, little is known of the complete structural interface of the heteromer. Through a mutational-based approach, previous research identified Transmembrane domain 4 (TM4) as being responsible for mediating heteromerization in mGlu2 before determining the particular amino acids responsible for the interface. A similar technique was used in this investigation to determine which component of 5-HT2A is responsible for the heterodimeric interface. Here, I identified four residues at the N-terminal of transmembrane domain four essential for the 5-HT2A receptor to form a GPCR heteromer with the mGlu2 receptor in HEK-293 cells. Substitution of these residues (phenylalanine 4.43, leucine 4.44, isoleucine 4.47, and alanine 4.48) leads to a significant reduction of 5-HT2A·mGlu2 receptor complex formation. This finding offers potential targets for future photo-crosslinking investigations to identify the particular residues within the 5-HT2A responsible for mediating the heteromeric interface of the 5-HT2A·mGlu2 complex.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
12-14-2021