Type 2β Corticotrophin Releasing Factor Receptor Forms a Heteromeric Complex With Dopamine D1 Receptor in Living Cells

Simple item page
dc.contributor.authorYarur, Hector E.
dc.contributor.authorEstela Andres, Maria
dc.contributor.authorGysling, Katia
dc.date.accessioned2025-01-23T19:56:48Z
dc.date.available2025-01-23T19:56:48Z
dc.date.issued2020
dc.description.abstractCorticotrophin releasing factor (CRF) and its related peptides differentially bind to CRF receptors to modulate stress-related behaviors. CRF receptors comprise two G-protein coupled receptors (GPCR), type-1 CRF receptors (CRF1), and type-2 CRF receptors (CRF2). CRF2 encompasses three spliced variants in humans, alpha (CRF2 alpha), beta (CRF2 beta), and gamma (CRF2 gamma), which differ in their N-terminal extracellular domains and expression patterns. Previously, we showed that CRF2 alpha form a heteromeric protein complex with dopamine D1 receptors (D1R), leading to changes in the signaling of D1R. Based on the high sequence identity between CRF2 alpha and CRF2 beta, we hypothesized that CRF2 beta also heteromerize with D1R. To test the hypothesis, we compared the expression and localization of both CRF2 isoforms and whether CRF2 beta form stable protein complexes with D1R in HEK293 and ATR75 cell lines. We observed that the immunoreactivity for CRF2 beta was similar to that of CRF2 alpha in the endoplasmic compartment but significantly higher in the Golgi compartment. Immunoprecipitation analysis showed that CRF2 beta forms a heteromeric protein complex with D1R. Furthermore, the protein complex formed by CRF2 beta and D1R was stable enough to change the sub-cellular localization of CRF2 beta when it was co-expressed with a construct of D1R bearing a nuclear localization signal. Immunofluorescence in A7R5 cells, which endogenously express CRF2 beta and D1R, shows significant colocalization of CRF2 beta with D1R. In conclusion, our results show that CRF2 beta forms a stable heteromeric protein complex with D1R, a potential new therapeutic target in tissues where both receptors are co-expressed, such as the septum in the brain, and heart, kidney, and skeletal muscle in the periphery.
dc.fuente.origenWOS
dc.identifier.doi10.3389/fphar.2019.01501
dc.identifier.eissn1663-9812
dc.identifier.urihttps://doi.org/10.3389/fphar.2019.01501
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/100716
dc.identifier.wosidWOS:000618702000001
dc.language.isoen
dc.revistaFrontiers in pharmacology
dc.rightsacceso restringido
dc.subjectD1R (dopamine D1 receptor)
dc.subjectheteromer
dc.subjectGPCR (G protein-coupled receptors
dc.subjectA7r5 cells
dc.subjectCRF2 beta
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleType 2β Corticotrophin Releasing Factor Receptor Forms a Heteromeric Complex With Dopamine D1 Receptor in Living Cells
dc.typeartículo
dc.volumen10
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
Files
Collections
Artículos de revistas