Helmholtz Gemeinschaft

Search
Browse
Statistics
Feeds

The coming together of allosteric and phosphorylation mechanisms in the molecular integration of A2A heteroreceptor complexes in the dorsal and ventral striatal-pallidal GABA neurons

[img]
Preview
PDF (Original Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
1MB

Item Type:Review
Title:The coming together of allosteric and phosphorylation mechanisms in the molecular integration of A2A heteroreceptor complexes in the dorsal and ventral striatal-pallidal GABA neurons
Creators Name:Borroto-Escuela, D.O. and Ferraro, L. and Beggiato, S. and Narváez, M. and Fores-Pons, R. and Alvarez-Contino, J.E. and Wydra, K. and Frankowska, M. and Bader, M. and Filip, M. and Fuxe, K.
Abstract:The role of adenosine A2A receptor (A2AR) and striatal-enriched protein tyrosine phosphatase (STEP) interactions in the striatal-pallidal GABA neurons was recently discussed in relation to A2AR overexpression and cocaine-induced increases of brain adenosine levels. As to phosphorylation, combined activation of A2AR and metabotropic glutamate receptor 5 (mGluR5) in the striatal-pallidal GABA neurons appears necessary for phosphorylation of the GluA1 unit of the AMPA receptor to take place. Robert Yasuda (J Neurochem 152: 270–272, 2020) focused on finding a general mechanism by which STEP activation is enhanced by increased A2AR transmission in striatal-pallidal GABA neurons expressing A2AR and dopamine D2 receptor. In his Editorial, he summarized in a clear way the significant effects of A2AR activation on STEP in the dorsal striatal-pallidal GABA neurons which involves a rise of intracellular levels of calcium causing STEP activation through its dephosphorylation. However, the presence of the A2AR in an A2AR-fibroblast growth factor receptor 1 (FGFR1) heteroreceptor complex can be required in the dorsal striatal-pallidal GABA neurons for the STEP activation. Furthermore, Won et al. (Proc Natl Acad Sci USA 116: 8028–8037, 2019) found in mass spectrometry experiments that the STEP splice variant STEP(61) can bind to mGluR5 and inactivate it. In addition, A2AR overexpression can lead to increased formation of A2AR-mGluR5 heterocomplexes in ventral striatal-pallidal GABA neurons. It involves enhanced facilitatory allosteric interactions leading to increased Gq-mediated mGluR5 signaling activating STEP. The involvement of both A2AR and STEP in the actions of cocaine on synaptic downregulation was also demonstrated. The enhancement of mGluR5 protomer activity by the A2AR protomer in A2AR-mGluR5 heterocomplexes in the nucleus accumbens shell appears to have a novel significant role in STEP mechanisms by both enhancing the activation of STEP and being a target for STEP(61).
Keywords:Adenosine A2A Receptor, Allosteric Receptor–Receptor Interactions, Cocaine, Oligomerization, Phosphorylation, Striatal-enriched Protein Tyrosine Phosphatase, Animals
Source:Pharmacological Reports
ISSN:1734-1140
Publisher:Institute of Pharmacology, Polish Academy of Sciences
Volume:73
Number:4
Page Range:1096-1108
Date:August 2021
Additional Information:Erratum in: Pharmacol Rep 73(5):1484.
Official Publication:https://doi.org/10.1007/s43440-021-00314-3
PubMed:View item in PubMed

Repository Staff Only: item control page

Downloads

Downloads per month over past year

Open Access
MDC Library