CRF binding protein facilitates the presence of CRF type 2 alpha receptor on the cell surface

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

dc.creatorSlater-Guzmán, Paula
dc.creatorCerda, Cledi A
dc.creatorPereira, Luis A
dc.creatorAndrés, María E
dc.creatorGysling-Caselli, Katia Cecilia
dc.date2021-08-23T22:58:55Z
dc.date2022-07-07T14:55:45Z
dc.date2021-08-23T22:58:55Z
dc.date2022-07-07T14:55:45Z
dc.date2016
dc.date.accessioned2023-08-22T09:53:22Z
dc.date.available2023-08-22T09:53:22Z
dc.identifier1150244
dc.identifier1150244
dc.identifierhttps://hdl.handle.net/10533/252445
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8337995
dc.descriptionCorticotropin releasing factor binding protein (CRF-BP) was originally recognized as CRF sequestering protein. However, its differential subcellular localization in different brain nuclei suggests that CRF-BP may have additional functions. There is evidence that CRF-BP potentiates CRF and urocortin 1 actions through CRF type 2 receptors (CRF2R). CRF2R is a G protein-coupled receptor (GPCR) that is found mainly intracellularly as most GPCRs. The access of GPCRs to the cell surface is tightly regulated by escort proteins. We hypothesized that CRF-BP binds to CRF2R, exerting an escort protein role. We analyzed the colocalization of CRF-BP and CRF2R in cultured rat mesencephalic neurons, and the localization and interaction of heterologous expressed CRF-BP and CRF2 alpha R in yeast, human embryonic kidney 293, and rat pheochromocytoma 12 cells. Our results showed that CRF-BP and CRF2R naturally colocalize in the neurites of cultured mesencephalic neurons. Heterologous expression of each protein showed that CRF-BP was localized mainly in secretory granules and CRF2 alpha R in the endoplasmic reticulum. In contrast, CRF-BP and CRF2 alpha R colocalized when both proteins are coexpressed. Here we show that CRF-BP physically interacts with the CRF2 alpha R but not the CRF2 beta R isoform, increasing CRF2 alpha R on the cell surface. Thus, CRF-BP emerges as a GPCR escort protein increasing the understanding of GPCR trafficking.
dc.descriptionRegular 2015
dc.descriptionFONDECYT
dc.descriptionFONDECYT
dc.languageeng
dc.relationhandle/10533/111557
dc.relationhandle/10533/111541
dc.relationhandle/10533/108045
dc.relationhttps://doi.org/10.1073/pnas.1523745113
dc.rightsAtribución-NoComercial-SinDerivadas 3.0 Chile
dc.rightshttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/
dc.rightsinfo:eu-repo/semantics/article
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleCRF binding protein facilitates the presence of CRF type 2 alpha receptor on the cell surface
dc.titlePROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
dc.typeArticulo
dc.typeinfo:eu-repo/semantics/publishedVersion


Este ítem pertenece a la siguiente institución