The GABA B receptor mediates neuroprotection by coupling to G 13 - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Science Signaling Année : 2021

The GABA B receptor mediates neuroprotection by coupling to G 13

Résumé

G protein–coupled receptors (GPCRs) activate various mitogen-activated protein kinase (MAPK) pathways to regulate critical cell functions. β-Arrestins mediate this mechanism for most GPCRs but not the GABAB receptor (GABABR). When coupled to the G protein Gi/o, GABABR phosphorylates the kinases ERK1 and ERK2. Here, we uncovered a distinct β-arrestin–independent mechanism of MAPK pathway activation by GABABR. We found that GABABR also phosphorylated the kinase JNK downstream of activation of the small guanosine triphosphatases (GTPases) RhoA and Rac1 in primary mouse neurons. However, instead of Gi/o proteins, activation of this RhoA/Rac1-JNK pathway was mediated by G13. This pathway promoted the phosphorylation and accumulation of the postsynaptic scaffolding protein PSD95 and GABABR-mediated neuroprotection in granule neurons. In addition, this pathway synergized with a previously reported GABABR-mediated neuroprotection mediated by a Gi/o-dependent mechanism. GABABR agonists activated G13 with slower kinetics and lower potency than with which they activated Gi/o. Our findings reveal distinct, β-arrestin–independent, context-specific synergistic mechanisms of MAPK activation by G protein–mediated GPCR signaling.
Fichier principal
Vignette du fichier
Wang GB-G13 SciSignal 2021.pdf (9.59 Mo) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)

Dates et versions

hal-03394399 , version 1 (17-11-2021)

Identifiants

Citer

Yunyun Wang, Siyu Gai, Wenhua Zhang, Xuetao Huang, Shumin Ma, et al.. The GABA B receptor mediates neuroprotection by coupling to G 13. Science Signaling, 2021, 14 (705), pp.eaaz4112. ⟨10.1126/scisignal.aaz4112⟩. ⟨hal-03394399⟩
29 Consultations
196 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More