{"has_accepted_license":"1","author":[{"orcid":"0000-0001-5297-733X","first_name":"Rouven","last_name":"Schulz","id":"4C5E7B96-F248-11E8-B48F-1D18A9856A87","full_name":"Schulz, Rouven"}],"doi":"10.15479/at:ista:11945","page":"133","publication_identifier":{"issn":["2663-337X"]},"citation":{"ieee":"R. Schulz, “Chimeric G protein-coupled receptors mimic distinct signaling pathways and modulate microglia function,” Institute of Science and Technology Austria, 2022.","mla":"Schulz, Rouven. <i>Chimeric G Protein-Coupled Receptors Mimic Distinct Signaling Pathways and Modulate Microglia Function</i>. Institute of Science and Technology Austria, 2022, doi:<a href=\"https://doi.org/10.15479/at:ista:11945\">10.15479/at:ista:11945</a>.","short":"R. Schulz, Chimeric G Protein-Coupled Receptors Mimic Distinct Signaling Pathways and Modulate Microglia Function, Institute of Science and Technology Austria, 2022.","chicago":"Schulz, Rouven. “Chimeric G Protein-Coupled Receptors Mimic Distinct Signaling Pathways and Modulate Microglia Function.” Institute of Science and Technology Austria, 2022. <a href=\"https://doi.org/10.15479/at:ista:11945\">https://doi.org/10.15479/at:ista:11945</a>.","ista":"Schulz R. 2022. Chimeric G protein-coupled receptors mimic distinct signaling pathways and modulate microglia function. Institute of Science and Technology Austria.","apa":"Schulz, R. (2022). <i>Chimeric G protein-coupled receptors mimic distinct signaling pathways and modulate microglia function</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:11945\">https://doi.org/10.15479/at:ista:11945</a>","ama":"Schulz R. Chimeric G protein-coupled receptors mimic distinct signaling pathways and modulate microglia function. 2022. doi:<a href=\"https://doi.org/10.15479/at:ista:11945\">10.15479/at:ista:11945</a>"},"_id":"11945","language":[{"iso":"eng"}],"year":"2022","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"}],"file_date_updated":"2022-08-25T09:33:31Z","project":[{"name":"Modulating microglia through G protein-coupled receptor (GPCR) signaling","_id":"267F75D8-B435-11E9-9278-68D0E5697425"}],"ddc":["570"],"type":"dissertation","file":[{"content_type":"application/pdf","creator":"rschulz","access_level":"open_access","file_name":"Thesis_Rouven_Schulz_2022_final.pdf","checksum":"61b1b666a210ff7cdd0e95ea75207a13","relation":"main_file","success":1,"file_id":"11970","file_size":28079331,"date_created":"2022-08-25T08:59:57Z","date_updated":"2022-08-25T08:59:57Z"},{"date_updated":"2022-08-25T09:33:31Z","file_id":"11971","file_size":27226963,"date_created":"2022-08-25T09:00:11Z","relation":"source_file","checksum":"2b8f95ea1c134dbdb927b41b1dbeeeb5","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_name":"Thesis_Rouven_Schulz_2022_final.docx","creator":"rschulz","access_level":"closed"}],"degree_awarded":"PhD","day":"23","supervisor":[{"orcid":"0000-0001-8635-0877","last_name":"Siegert","first_name":"Sandra","full_name":"Siegert, Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87"}],"month":"08","article_processing_charge":"No","date_updated":"2023-08-03T13:02:26Z","tmp":{"image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"publication_status":"published","date_published":"2022-08-23T00:00:00Z","department":[{"_id":"GradSch"},{"_id":"SaSi"}],"abstract":[{"text":"G protein-coupled receptors (GPCRs) respond to specific ligands and regulate multiple processes ranging from cell growth and immune responses to neuronal signal transmission. However, ligands for many GPCRs remain unknown, suffer from off-target effects or have poor bioavailability. Additional challenges exist to dissect cell-type specific responses when the same GPCR is expressed on several cell types within the body. Here, we overcome these limitations by engineering DREADD-based GPCR chimeras that selectively bind their agonist clozapine-N-oxide (CNO) and mimic a GPCR-of-interest in a desired cell type.\r\nWe validated our approach with β2-adrenergic receptor (β2AR/ADRB2) and show that our chimeric DREADD-β2AR triggers comparable responses on second messenger and kinase activity, post-translational modifications, and protein-protein interactions. Since β2AR is also enriched in microglia, which can drive inflammation in the central nervous system, we expressed chimeric DREADD-β2AR in primary microglia and successfully recapitulate β2AR-mediated filopodia formation through CNO stimulation. To dissect the role of selected GPCRs during microglial inflammation, we additionally generated DREADD-based chimeras for microglia-enriched GPR65 and GPR109A/HCAR2. In a microglia cell line, DREADD-β2AR and DREADD-GPR65 both modulated the inflammatory response with a similar profile as endogenously expressed β2AR, while DREADD-GPR109A showed no impact.\r\nOur DREADD-based approach provides the means to obtain mechanistic and functional insights into GPCR signaling on a cell-type specific level.","lang":"eng"}],"oa_version":"Published Version","oa":1,"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","date_created":"2022-08-23T11:33:11Z","publisher":"Institute of Science and Technology Austria","title":"Chimeric G protein-coupled receptors mimic distinct signaling pathways and modulate microglia function","status":"public","related_material":{"record":[{"relation":"dissertation_contains","id":"11995","status":"public"}]},"alternative_title":["ISTA Thesis"]}