Role of cystic fibrosis transmembrane conductance regulator-associated ligand (CAL) in regulating the trafficking and signaling of corticotropin-releasing factor receptor 1.

Role of cystic fibrosis transmembrane conductance regulator-associated ligand (CAL) in regulating the trafficking and signaling of corticotropin-releasing factor receptor 1. Cell Signal. 2015 Jun 23; Authors: Hammad MM, Dunn HA, Walther C, Ferguson SS Abstract Corticotropin releasing factor (CRF) receptor1 (CRFR1) is associated with psychiatric illness and is a proposed target for the treatment of anxiety and depression. Like many G protein-coupled receptors (GPCRs), CRFR1 harbors a PDZ (PSD-95/Disc Large/Zona Occludens 1)-binding motif at the end of its carboxyl terminal tail. The interactions of PDZ proteins with GPCRs is crucial for the regulation of their receptor function. In the present study, we characterize the interaction of the cystic fibrosis transmembrane conductance regulator-associated ligand (CAL) with CRFR1. We show using co-immunoprecipitation that the two proteins interact in human embryonic kidney (HEK293) cells in a PDZ motif-dependent manner. We find that the interaction occurs at the Golgi apparatus and that overexpression of CAL retains a proportion of CRFR1 in the intracellular compartment and reduces trafficking to the cell surface. We also demonstrate a significant reduction in the levels of receptor at the plasma membrane upon CAL overexpression, as well as a reduction in internalization. We find that the overexpression of CAL in HEK293 cells resulted in a significant reduction in CRF-stimulated extracellul...
Source: Cellular Signalling - Category: Cytology Authors: Tags: Cell Signal Source Type: research