Arrestin-independent constitutive endocytosis of GPR125/ADGRA3
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Arrestin-independent constitutive endocytosis of GPR125/ADGRA3. / Spiess, Katja; Bagger, Sofie O.; Torz, Lola J.; Jensen, Kristian H. R.; Walser, Anna L.; Kvam, Jone M.; Mogelmose, Ann-Sofie K.; Daugvilaite, Viktorija; Junnila, Riia K.; Hjorto, Gertrud M.; Rosenkilde, Mette M.
In: Annals of the New York Academy of Sciences, Vol. 1456, 2019, p. 186–199 .Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Arrestin-independent constitutive endocytosis of GPR125/ADGRA3
AU - Spiess, Katja
AU - Bagger, Sofie O.
AU - Torz, Lola J.
AU - Jensen, Kristian H. R.
AU - Walser, Anna L.
AU - Kvam, Jone M.
AU - Mogelmose, Ann-Sofie K.
AU - Daugvilaite, Viktorija
AU - Junnila, Riia K.
AU - Hjorto, Gertrud M.
AU - Rosenkilde, Mette M.
PY - 2019
Y1 - 2019
N2 - 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 β‐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 β‐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.
AB - 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 β‐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 β‐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.
KW - adhesion GPCR
KW - GPR125
KW - ADGRA3
KW - internalization
KW - endocytosis
KW - beta-arrestin
U2 - 10.1111/nyas.14263
DO - 10.1111/nyas.14263
M3 - Journal article
C2 - 31659746
VL - 1456
SP - 186
EP - 199
JO - Annals of The Lyceum of Natural History of New York
JF - Annals of The Lyceum of Natural History of New York
SN - 0077-8923
ER -
ID: 230039964