| First Author | Mototani Y | Year | 2018 |
| Journal | Pflugers Arch | Volume | 470 |
| Issue | 6 | Pages | 937-947 |
| PubMed ID | 29500670 | Mgi Jnum | J:302084 |
| Mgi Id | MGI:6507633 | Doi | 10.1007/s00424-018-2124-1 |
| Citation | Mototani Y, et al. (2018) Role of G protein-regulated inducer of neurite outgrowth 3 (GRIN3) in beta-arrestin 2-Akt signaling and dopaminergic behaviors. Pflugers Arch 470(6):937-947 |
| abstractText | The G protein-regulated inducer of neurite growth (GRIN) family has three isoforms (GRIN1-3), which bind to the Galphai/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)-beta-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 beta-arrestins 1/2. Among GRINs, only GRIN3, which is highly expressed in striatum, strongly interacted with beta-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 beta-arrestin 2-mediated pathway. Dephosphorylation of phospho308-Akt via the D2R-beta-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 beta-arrestin-dependent, G protein-independent signaling. |
