Role of G protein-regulated inducer of neurite outgrowth 3 (GRIN3) in β-arrestin 2-Akt signaling and dopaminergic behaviors
| Autor: | Aiko Ito, Yasutake Saeki, Daisuke Umeki, Motohito Goto, Yoshinori Sahara, Tohru Kozasa, Kouichi Shiozawa, Tadashi Okamura, Yuka Yagisawa, Yoshiki Ohnuki, Rieko Yanobu-Takanashi, Naoya Kawamura, Yukiko Shimizu, Yasumasa Mototani, Megumi Nariyama, Kenji Suita, Satoshi Okumura |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Neurite Physiology G protein Clinical Biochemistry Nerve Tissue Proteins Anxiety Receptors Dopamine Mice 03 medical and health sciences Physiology (medical) Animals Humans Maze Learning Protein kinase B beta-Arrestins G protein-coupled receptor Binding Sites Chemistry Dopaminergic Corpus Striatum Cell biology Mice Inbred C57BL HEK293 Cells 030104 developmental biology Dopamine receptor Phosphorylation Signal transduction Proto-Oncogene Proteins c-akt Locomotion Protein Binding Signal Transduction |
| Zdroj: | Pflügers Archiv - European Journal of Physiology. 470:937-947 |
| ISSN: | 1432-2013 0031-6768 |
| Popis: | The G protein-regulated inducer of neurite growth (GRIN) family has three isoforms (GRIN1-3), which bind to the Gαi/o subfamily of G protein that mediate signal processing via G protein-coupled receptors (GPCRs). Here, we show that GRIN3 is involved in regulation of dopamine-dependent behaviors and is essential for activation of the dopamine receptors (DAR)-β-arrestin signaling cascade. Analysis of functional regions of GRIN3 showed that a di-cysteine motif (Cys751/752) is required for plasma membrane localization. GRIN3 was co-immunoprecipitated with GPCR kinases 2/6 and β-arrestins 1/2. Among GRINs, only GRIN3, which is highly expressed in striatum, strongly interacted with β-arrestin 2. We also generated GRIN3-knockout mice (GRIN3KO). GRIN3KO exhibited reduced locomotor activity and increased anxiety-like behavior in the elevated maze test, as well as a reduced locomoter response to dopamine stimulation. We also examined the phosphorylation of Akt at threonine 308 (phospho308-Akt), which is dephosphorylated via a β-arrestin 2-mediated pathway. Dephosphorylation of phospho308-Akt via the D2R-β-arrestin 2 signaling pathway was completely abolished in striatum of GRIN3KO. Our results suggest that GRIN3 has a role in recruitment and assembly of proteins involved in β-arrestin-dependent, G protein-independent signaling. |
| Databáze: | OpenAIRE |
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