Distinct cellular and subcellular distributions of G protein-coupled receptor kinase and arrestin isoforms in the striatum

G protein-coupled receptor kinases (GRKs) and arrestins mediate desensitization of G protein-coupled receptors (GPCR). Arrestins also mediate G protein-independent signaling via GPCRs. Since GRK and arrestins demonstrate no strict receptor specificity, their functions in the brain may depend on thei...

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Bibliographic Details
Published in:PloS one 2012-11, Vol.7 (11), p.e48912-e48912
Main Authors: Bychkov, Evgeny, Zurkovsky, Lilia, Garret, Mika B, Ahmed, Mohamed R, Gurevich, Eugenia V
Format: Article
Language:English
Subjects:
Animals
Arrestin
Arrestin - metabolism
b-Adrenergic-receptor kinase
Biology
Brain
Cell Nucleus - enzymology
Cholinergic Neurons - cytology
Cholinergic Neurons - enzymology
Desensitization
Female
G protein-coupled receptor kinase
G protein-coupled receptors
G proteins
G-Protein-Coupled Receptor Kinases - metabolism
Humans
Interneurons
Interneurons - cytology
Interneurons - enzymology
Isoenzymes - metabolism
Isoforms
Kinases
Laboratory animals
Localization
Male
Membrane proteins
Membranes
Middle Aged
Neostriatum
Neostriatum - cytology
Neostriatum - enzymology
Neurons
Nuclei (cytology)
Parvalbumin
Phosphorylation
Protein Transport
Proteins
Rats
Rats, Sprague-Dawley
Receptors
Rodents
Signal transduction
Signaling
Spiny neurons
Subcellular Fractions - enzymology
Synaptic membranes
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Summary:G protein-coupled receptor kinases (GRKs) and arrestins mediate desensitization of G protein-coupled receptors (GPCR). Arrestins also mediate G protein-independent signaling via GPCRs. Since GRK and arrestins demonstrate no strict receptor specificity, their functions in the brain may depend on their cellular complement, expression level, and subcellular targeting. However, cellular expression and subcellular distribution of GRKs and arrestins in the brain is largely unknown. We show that GRK isoforms GRK2 and GRK5 are similarly expressed in direct and indirect pathway neurons in the rat striatum. Arrestin-2 and arrestin-3 are also expressed in neurons of both pathways. Cholinergic interneurons are enriched in GRK2, arrestin-3, and GRK5. Parvalbumin-positive interneurons express more of GRK2 and less of arrestin-2 than medium spiny neurons. The GRK5 subcellular distribution in the human striatal neurons is altered by its phosphorylation: unphosphorylated enzyme preferentially localizes to synaptic membranes, whereas phosphorylated GRK5 is found in plasma membrane and cytosolic fractions. Both GRK isoforms are abundant in the nucleus of human striatal neurons, whereas the proportion of both arrestins in the nucleus was equally low. However, overall higher expression of arrestin-2 yields high enough concentration in the nucleus to mediate nuclear functions. These data suggest cell type- and subcellular compartment-dependent differences in GRK/arrestin-mediated desensitization and signaling.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0048912