Arrestin-independent constitutive endocytosis of GPR125/ADGRA3.
Ann N Y Acad Sci
; 1456(1): 186-199, 2019 11.
Article
em En
| MEDLINE
| ID: mdl-31659746
ABSTRACT
The orphan receptor GPR125 (ADGRA3) belongs to subgroup III of the adhesion G protein-coupled receptor (aGPCR) family. aGPCRs, also known as class B2 GPCRs, share basic structural and functional properties with other GPCRs. Many of them couple to G proteins and activate G protein-dependent and -independent signaling pathways, but little is known about aGPCR internalization and ß-arrestin recruitment. GPR125 was originally described as a spermatogonial stem cell marker and studied for its role in Wnt signaling and cell polarity. Here, using cell-based assays and confocal microscopy, we show that GPR125 is expressed on the cell surface and undergoes constitutive endocytosis in a ß-arrestin-independent, but clathrin-dependent manner, as indicated by colocalization with transferrin receptor 1, an early endosome marker. These data support that the constitutive internalization of GPR125 contributes to its biological functions by controlling receptor surface expression and accessibility for ligands. Our study sheds light on a new property of aGPCRs, namely internalization; a property described to be important for signal propagation, signal termination, and desensitization of class A (rhodopsin-like) and B1 (VIP/secretin) GPCRs.
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Base de dados:
MEDLINE
Assunto principal:
Receptores Acoplados a Proteínas G
/
Endocitose
Limite:
Humans
Idioma:
En
Revista:
Ann N Y Acad Sci
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Dinamarca