title: Potential role of G protein-coupled receptor (GPCR) heterodimerization in neuropsychiatric disorders: a focus on depression.
abstract: G protein-coupled receptors (GPCRs) represent the largest family of membrane proteins in the human genome and are the target of approximately half of all therapeutic drugs. For many years, GPCRs were thought to exist and function as monomeric units. However, during the past two decades, substantial biochemical, structural and functional evidence have indicated that GPCRs can associate and form heteromers that exhibit functional properties distinct from the corresponding monomers. The understanding of the unique pharmacological and functional properties of such heteromers is a major challenge for neuroscience, particularly given the abundant evidence suggesting that GPCR heteromers may play a crucial role in neuropsychiatric disorders. Herein, we present current data on the role of GPCR heterodimerization in neuropsychiatric disorders, with a focus on its potential implications in depression. The presented examples of pairs of receptors, with their specific pharmacological and functional properties, are likely to lead to novel effective strategies in antidepressant drug development. The currently available techniques for studying GPCR heterodimerization, both in vitro as well as in situ in native tissue, are also described.
authors.affiliation: Laboratory of Biochemical Pharmacology, Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland. marta.wasylewska@gmail.com.
authors.forename: Kinga
authors.initials: K
authors.lastname: Szafran
authors.forename: Agata
authors.initials: A
authors.lastname: Faron-Górecka
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kolasa
authors.forename: Maciej
authors.initials: M
authors.lastname: Kuśmider
authors.forename: Joanna
authors.initials: J
authors.lastname: Solich
authors.forename: Dariusz
authors.initials: D
authors.lastname: Zurawek
authors.forename: Marta
authors.initials: M
authors.lastname: Dziedzicka-Wasylewska
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy / Q000378:metabolism*; D019281:Dimerization; D006801:Humans; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*
chemical_list: D000928:Antidepressive Agents; D043562:Receptors, G-Protein-Coupled