Chimeric G protein-coupled receptors mimic distinct signaling pathways and modulate microglia function (Record no. 655776)
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| 000 -LEADER | |
|---|---|
| fixed length control field | 02725ntm a22003617a 4500 |
| 003 - CONTROL NUMBER IDENTIFIER | |
| control field | AT-ISTA |
| 005 - DATE AND TIME OF LATEST TRANSACTION | |
| control field | 20230622112840.0 |
| 008 - FIXED-LENGTH DATA ELEMENTS--GENERAL INFORMATION | |
| fixed length control field | 230622s2022 au ||||| m||| 00| 0 eng d |
| 040 ## - CATALOGING SOURCE | |
| Transcribing agency | ISTA |
| 100 ## - MAIN ENTRY--PERSONAL NAME | |
| Personal name | Schulz, Rouven |
| 9 (RLIN) | 972371 |
| 245 ## - TITLE STATEMENT | |
| Title | Chimeric G protein-coupled receptors mimic distinct signaling pathways and modulate microglia function |
| 260 ## - PUBLICATION, DISTRIBUTION, ETC. (IMPRINT) | |
| Name of publisher, distributor, etc. | Institute of Science and Technology Austria |
| Date of publication, distribution, etc. | 2022 |
| 500 ## - GENERAL NOTE | |
| General note | Thesis |
| 505 ## - FORMATTED CONTENTS NOTE | |
| Formatted contents note | Abstract |
| 505 ## - FORMATTED CONTENTS NOTE | |
| Formatted contents note | Acknowledgments |
| 505 ## - FORMATTED CONTENTS NOTE | |
| Formatted contents note | About the Author |
| 505 ## - FORMATTED CONTENTS NOTE | |
| Formatted contents note | List of Contributors |
| 505 ## - FORMATTED CONTENTS NOTE | |
| Formatted contents note | List of Figures |
| 505 ## - FORMATTED CONTENTS NOTE | |
| Formatted contents note | List of Tables |
| 505 ## - FORMATTED CONTENTS NOTE | |
| Formatted contents note | List of Abbreviations |
| 505 ## - FORMATTED CONTENTS NOTE | |
| Formatted contents note | List of statistical terms and definitions |
| 505 ## - FORMATTED CONTENTS NOTE | |
| Formatted contents note | List of software packages for data visualization and statistical analysis |
| 505 ## - FORMATTED CONTENTS NOTE | |
| Formatted contents note | 1 Introduction |
| 505 ## - FORMATTED CONTENTS NOTE | |
| Formatted contents note | 2 Methods |
| 505 ## - FORMATTED CONTENTS NOTE | |
| Formatted contents note | 3 Results |
| 505 ## - FORMATTED CONTENTS NOTE | |
| Formatted contents note | 4 Discussion |
| 505 ## - FORMATTED CONTENTS NOTE | |
| Formatted contents note | 5 Supplementary Figures |
| 505 ## - FORMATTED CONTENTS NOTE | |
| Formatted contents note | 6 Supplementary Tables |
| 505 ## - FORMATTED CONTENTS NOTE | |
| Formatted contents note | 7 References |
| 520 ## - SUMMARY, ETC. | |
| Summary, etc. | 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. We 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. Our DREADD-based approach provides the means to obtain mechanistic and functional insights into GPCR signaling on a cell-type specific level. |
| 856 ## - ELECTRONIC LOCATION AND ACCESS | |
| Uniform Resource Identifier | <a href="https://doi.org/10.15479/at:ista:11945">https://doi.org/10.15479/at:ista:11945</a> |
| 942 ## - ADDED ENTRY ELEMENTS (KOHA) | |
| Source of classification or shelving scheme | Dewey Decimal Classification |
| Withdrawn status | Lost status | Source of classification or shelving scheme | Damaged status | Not for loan | Home library | Current library | Date acquired | Total Checkouts | Full call number | Barcode | Date last seen | Price effective from | Koha item type |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Not Lost | Dewey Decimal Classification | Library | Library | 22/06/2023 | Quiet Room | AT-ISTA#002807 | 15/09/2025 | 22/06/2023 | Book |