Increased G protein-coupled receptor kinase (GRK) expression in the anterior cingulate cortex in schizophrenia
Language: 
English
Abstract: 

BACKGROUND: Current pharmacological treatments for schizophrenia target G protein-coupled receptors (GPCRs), including dopamine receptors. Ligand-bound GPCRs are regulated by a family of G protein-coupled receptor kinases (GRKs), members of which uncouple the receptor from heterotrimeric G proteins, desensitize the receptor, and induce receptor internalization via the arrestin family of scaffolding and signaling molecules. GRKs initiate the activation of downstream signaling pathways, can regulate receptors and signaling molecules independent of GPCR phosphorylation, and modulate epigenetic regulators like histone deacetylases (HDACs). We hypothesize that the expression of GRK proteins is altered in schizophrenia, consistent with previous findings of alterations upstream and downstream from this family of molecules that facilitate intracellular signaling processes. METHODS: In this study, we measured protein expression via Western blot analysis for GRKs 2, 3, 5, and 6 in the anterior cingulate cortex of patients with schizophrenia (n=36) and a comparison group (n=33). To control for antipsychotic treatment, we measured these same targets in haloperidol-treated vs. untreated rats (n=10 for both). RESULTS: We found increased levels of GRK5 in schizophrenia. No changes were detected in GRK protein expression in rats treated with haloperidol decanoate for 9 months. CONCLUSION: These data suggest that increased GRK5 expression may contribute to the pathophysiology of schizophrenia via abnormal regulation of the cytoskeleton, endocytosis, signaling, GPCRs, and histone modification.

Author(s): 
Funk, Adam J.
Haroutunian, Vahram
Meador-Woodruff, James H.
McCullumsmith, Robert E.
Item Type: 
Journal Article
Publication Title: 
Schizophrenia Research
Journal Abbreviation: 
Schizophr. Res.
Publication Date: 
2014-10
Publication Year: 
2014
Pages: 
130-135
Volume: 
159
Issue: 
1
ISSN: 
1573-2509
DOI: 
10.1016/j.schres.2014.07.040
Library Catalog: 
PubMed
Extra: 
PMID: 25153362 PMCID: PMC4177355

Turabian/Chicago Citation

Adam J. Funk, Vahram Haroutunian, James H. Meador-Woodruff and Robert E. McCullumsmith. 2014-10. "Increased G protein-coupled receptor kinase (GRK) expression in the anterior cingulate cortex in schizophrenia." Schizophrenia Research 159: 1: 130-135. 10.1016/j.schres.2014.07.040.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1016/j.schres.2014.07.040 | issn = 1573-2509 | volume = 159 | pages = 130-135 | last = Funk | first = Adam J. | coauthors = Haroutunian, Vahram, Meador-Woodruff, James H., McCullumsmith, Robert E. | title = Increased G protein-coupled receptor kinase (GRK) expression in the anterior cingulate cortex in schizophrenia | journal = Schizophrenia Research | date = 2014-10 | pmid = | pmc = }} </ref>