DOI

https://doi.org/10.25772/CK61-1E46

Author ORCID Identifier

https://orcid.org/0000-0003-3072-5312

Defense Date

2020

Document Type

Thesis

Degree Name

Master of Science

Department

Physiology and Biophysics

First Advisor

Javier Gonzalez-Maeso

Second Advisor

Srinivasa Karnam

Third Advisor

Sammanda Ramamoorthy

Abstract

Schizophrenia is a serious mental disorder characteristic of several neurotransmitters including dopamine, serotonin, and glutamate being in imbalance. Early therapies focused solely on dopamine antagonism and second-generation antipsychotics focused on the dopamine and serotonin systems and their respective G protein coupled receptor (GPCR) proteins. Although debate for dimerization of certain classes of GPCR exist, the establishment of an mGlu2-5-HT2A heterocomplex, which is implicated in schizophrenia is of interest. Previous studies have used a mutation-based approach to identify transmembrane domain 4 (TM4) as the domain responsible in mGlu2 for mediating heteromerization before narrowing down the individual amino acids responsible for the interface. A similar approach to consider which portion of 5-HT2A is responsible for the heterodimeric interface was used in this study. We confirm that wild type 5-HT2A and mGlu2 coimmunoprecipitate. Two 5-HT2A chimeric constructs involving full and partial N terminal half TM4 mutations were created using aligned residues of 5-HT2C (which is unable to dimerize with mGlu2). In addition to providing valuable insight into the structural arrangement of GPCR heteromers involving different families, these findings offer future direction for photo-crosslinking experiments aiming to identify individual amino acids within the 5-HT2A responsible for mediating the heteromeric interface of the mGlu2-5-HT2A complex.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

5-14-2020

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