{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:29:26Z","timestamp":1786408166441,"version":"build-2736575974"},"reference-count":57,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100011033","name":"Agencia Estatal de Investigaci\u00f3n","doi-asserted-by":"publisher","award":["PID2021\u2010126600OB\u2010I00"],"award-info":[{"award-number":["PID2021\u2010126600OB\u2010I00"]}],"id":[{"id":"10.13039\/501100011033","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Glia"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    G protein\u2013coupled receptor (GPCR) heteromerization represents a key organizational mechanism in cell signaling, but it remains difficult to determine, in native cells, how receptor\u2010associated signals are distributed between non\u2010interacting and heteromer\u2010associated states. Here, we address this limitation by combining proximity ligation assay (PLA) with the newly applied MolBoolean methodology, enabling in\u00a0situ quantification of the partitioning of adenosine A\n                    <jats:sub>2A<\/jats:sub>\n                    and cannabinoid CB\n                    <jats:sub>2<\/jats:sub>\n                    receptor\u2010associated signals between non\u2010interacting fractions and A\n                    <jats:sub>2A<\/jats:sub>\n                    \u2013CB\n                    <jats:sub>2<\/jats:sub>\n                    heteromeric complexes in primary microglia. We show that resting microglia contain detectable A\n                    <jats:sub>2A<\/jats:sub>\n                    \u2013CB\n                    <jats:sub>2<\/jats:sub>\n                    heteromers together with a substantial non\u2010interacting A\n                    <jats:sub>2A<\/jats:sub>\n                    \u2010associated signal fraction. Selective activation of either receptor promotes redistribution of the detectable receptor\u2010associated signal toward the heteromer\u2010associated fraction. Ligand\u2010induced redistribution also occurred in HEK\u2010293T cells expressing the two receptors. In contrast, pro\u2010inflammatory activation of primary microglia with LPS\/IFN\u2010\u03b3 markedly changes the basal organization of the receptor system, increasing the proportion of MolBoolean\u2010detectable signal associated with A\n                    <jats:sub>2A<\/jats:sub>\n                    \u2013CB\n                    <jats:sub>2<\/jats:sub>\n                    complexes, with approximately 70% of the detectable receptor\u2010associated signal corresponding to heteromeric complexes. In this inflammatory context, further agonist\u2010induced repartitioning is strongly limited compared with that observed in resting microglia. These findings identify inflammation\u2010dependent receptor partitioning as a quantitatively measurable feature of microglial A\n                    <jats:sub>2A<\/jats:sub>\n                    and CB\n                    <jats:sub>2<\/jats:sub>\n                    receptor organization and provide a framework for interpreting how receptor context may influence future studies of A\n                    <jats:sub>2A<\/jats:sub>\n                    \u2013CB\n                    <jats:sub>2<\/jats:sub>\n                    pharmacology under neuroinflammatory conditions.\n                  <\/jats:p>","DOI":"10.1002\/glia.70200","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T05:36:38Z","timestamp":1784698598000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Quantifying Heteromer Partitioning Reveals Inflammation\u2010Dependent Redistribution of Microglial Adenosine\n                    <scp>\n                      A\n                      <sub>2A<\/sub>\n                    <\/scp>\n                    and Cannabinoid\n                    <scp>\n                      CB\n                      <sub>2<\/sub>\n                    <\/scp>\n                    Receptors"],"prefix":"10.1002","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2549-4919","authenticated-orcid":false,"given":"Rafael","family":"Franco","sequence":"first","affiliation":[{"name":"CIBERNED (Center for Networked Biomedical Research on Neurodegenerative Diseases), Spanish National Institute of Health Carlos III  Madrid Spain"},{"name":"Department of Biochemistry and Molecular Biomedicine University of Barcelona  Barcelona Spain"},{"name":"Institute of Theoretical and Computational Chemistry (IQTCUB), School of Chemistry, University of Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaume","family":"Lillo","sequence":"additional","affiliation":[{"name":"CIBERNED (Center for Networked Biomedical Research on Neurodegenerative Diseases), Spanish National Institute of Health Carlos III  Madrid Spain"},{"name":"Department of Biochemistry and Physiology University of Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5424-9130","authenticated-orcid":false,"given":"Christian","family":"Gri\u00f1\u00e1n\u2010Ferr\u00e9","sequence":"additional","affiliation":[{"name":"CIBERNED (Center for Networked Biomedical Research on Neurodegenerative Diseases), Spanish National Institute of Health Carlos III  Madrid Spain"},{"name":"Department of Pharmacology and Therapeutic Chemistry Institute of Neurosciences\u2013University of Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merc\u00e8","family":"Pall\u00e0s","sequence":"additional","affiliation":[{"name":"CIBERNED (Center for Networked Biomedical Research on Neurodegenerative Diseases), Spanish National Institute of Health Carlos III  Madrid Spain"},{"name":"Department of Pharmacology and Therapeutic Chemistry Institute of Neurosciences\u2013University of Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2078-6819","authenticated-orcid":false,"given":"Rafael","family":"Rivas\u2010Santisteban","sequence":"additional","affiliation":[{"name":"CIBERNED (Center for Networked Biomedical Research on Neurodegenerative Diseases), Spanish National Institute of Health Carlos III  Madrid Spain"},{"name":"Department of Biochemistry and Molecular Biomedicine University of Barcelona  Barcelona Spain"},{"name":"Institute of Theoretical and Computational Chemistry (IQTCUB), School of Chemistry, University of Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"key":"e_1_2_10_2_1","first-page":"183","article-title":"New Vistas on Synaptic Plasticity: The Receptor Mosaic Hypothesis of the Engram","volume":"60","author":"Agnati L. 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