Migration mediated by the oxysterol receptor GPR183 depends on arrestin coupling but not receptor internalization

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Standard

Migration mediated by the oxysterol receptor GPR183 depends on arrestin coupling but not receptor internalization. / Kjær, Viktoria M. S.; Daugvilaite, Viktorija; Stepniewski, Tomasz M.; Madsen, Christian M.; Jørgensen, Astrid S.; Bhuskute, Kaustubh R.; Inoue, Asuka; Ulven, Trond; Benned-Jensen, Tau; Hjorth, Siv A.; Hjortø, Gertrud M.; Moo, Ee Von; Selent, Jana; Rosenkilde, Mette M.

In: Science Signaling, Vol. 16, No. 779, eabl4283, 2023.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Kjær, VMS, Daugvilaite, V, Stepniewski, TM, Madsen, CM, Jørgensen, AS, Bhuskute, KR, Inoue, A, Ulven, T, Benned-Jensen, T, Hjorth, SA, Hjortø, GM, Moo, EV, Selent, J & Rosenkilde, MM 2023, 'Migration mediated by the oxysterol receptor GPR183 depends on arrestin coupling but not receptor internalization', Science Signaling, vol. 16, no. 779, eabl4283. https://doi.org/10.1126/scisignal.abl4283

APA

Kjær, V. M. S., Daugvilaite, V., Stepniewski, T. M., Madsen, C. M., Jørgensen, A. S., Bhuskute, K. R., Inoue, A., Ulven, T., Benned-Jensen, T., Hjorth, S. A., Hjortø, G. M., Moo, E. V., Selent, J., & Rosenkilde, M. M. (2023). Migration mediated by the oxysterol receptor GPR183 depends on arrestin coupling but not receptor internalization. Science Signaling, 16(779), [eabl4283]. https://doi.org/10.1126/scisignal.abl4283

Vancouver

Kjær VMS, Daugvilaite V, Stepniewski TM, Madsen CM, Jørgensen AS, Bhuskute KR et al. Migration mediated by the oxysterol receptor GPR183 depends on arrestin coupling but not receptor internalization. Science Signaling. 2023;16(779). eabl4283. https://doi.org/10.1126/scisignal.abl4283

Author

Kjær, Viktoria M. S. ; Daugvilaite, Viktorija ; Stepniewski, Tomasz M. ; Madsen, Christian M. ; Jørgensen, Astrid S. ; Bhuskute, Kaustubh R. ; Inoue, Asuka ; Ulven, Trond ; Benned-Jensen, Tau ; Hjorth, Siv A. ; Hjortø, Gertrud M. ; Moo, Ee Von ; Selent, Jana ; Rosenkilde, Mette M. / Migration mediated by the oxysterol receptor GPR183 depends on arrestin coupling but not receptor internalization. In: Science Signaling. 2023 ; Vol. 16, No. 779.

Bibtex

@article{84f27999adbd450b943ae60ce43c85b8,
title = "Migration mediated by the oxysterol receptor GPR183 depends on arrestin coupling but not receptor internalization",
abstract = "The chemotactic G protein–coupled receptor GPR183 and its most potent endogenous oxysterol ligand 7α,25-dihydroxycholesterol (7α,25-OHC) are important for immune cell positioning in secondary lymphoid tissues. This receptor-ligand pair is associated with various diseases, in some cases contributing favorably and in other cases adversely, making GPR183 an attractive target for therapeutic intervention. We investigated the mechanisms underlying GPR183 internalization and the role of internalization in the main biological function of the receptor, chemotaxis. We found that the C terminus of the receptor was important for ligand-induced internalization but less so for constitutive (ligand-independent) internalization. β-arrestin potentiated ligand-induced internalization but was not required for ligand-induced or constitutive internalization. Caveolin and dynamin were the main mediators of both constitutive and ligand-induced receptor internalization in a mechanism independent of G protein activation. Clathrin-mediated endocytosis also contributed to constitutive GPR183 internalization in a β-arrestin–independent manner, suggesting the existence of different pools of surface-localized GPR183. Chemotaxis mediated by GPR183 depended on receptor desensitization by β-arrestins but could be uncoupled from internalization, highlighting an important biological role for the recruitment of β-arrestin to GPR183. The role of distinct pathways in internalization and chemotaxis may aid in the development of GPR183-targeting drugs for specific disease contexts.",
author = "Kj{\ae}r, {Viktoria M. S.} and Viktorija Daugvilaite and Stepniewski, {Tomasz M.} and Madsen, {Christian M.} and J{\o}rgensen, {Astrid S.} and Bhuskute, {Kaustubh R.} and Asuka Inoue and Trond Ulven and Tau Benned-Jensen and Hjorth, {Siv A.} and Hjort{\o}, {Gertrud M.} and Moo, {Ee Von} and Jana Selent and Rosenkilde, {Mette M.}",
note = "Publisher Copyright: {\textcopyright} 2023 The Authors.",
year = "2023",
doi = "10.1126/scisignal.abl4283",
language = "English",
volume = "16",
journal = "Science Signaling",
issn = "1945-0877",
publisher = "American Association for the Advancement of Science",
number = "779",

}

RIS

TY - JOUR

T1 - Migration mediated by the oxysterol receptor GPR183 depends on arrestin coupling but not receptor internalization

AU - Kjær, Viktoria M. S.

AU - Daugvilaite, Viktorija

AU - Stepniewski, Tomasz M.

AU - Madsen, Christian M.

AU - Jørgensen, Astrid S.

AU - Bhuskute, Kaustubh R.

AU - Inoue, Asuka

AU - Ulven, Trond

AU - Benned-Jensen, Tau

AU - Hjorth, Siv A.

AU - Hjortø, Gertrud M.

AU - Moo, Ee Von

AU - Selent, Jana

AU - Rosenkilde, Mette M.

N1 - Publisher Copyright: © 2023 The Authors.

PY - 2023

Y1 - 2023

N2 - The chemotactic G protein–coupled receptor GPR183 and its most potent endogenous oxysterol ligand 7α,25-dihydroxycholesterol (7α,25-OHC) are important for immune cell positioning in secondary lymphoid tissues. This receptor-ligand pair is associated with various diseases, in some cases contributing favorably and in other cases adversely, making GPR183 an attractive target for therapeutic intervention. We investigated the mechanisms underlying GPR183 internalization and the role of internalization in the main biological function of the receptor, chemotaxis. We found that the C terminus of the receptor was important for ligand-induced internalization but less so for constitutive (ligand-independent) internalization. β-arrestin potentiated ligand-induced internalization but was not required for ligand-induced or constitutive internalization. Caveolin and dynamin were the main mediators of both constitutive and ligand-induced receptor internalization in a mechanism independent of G protein activation. Clathrin-mediated endocytosis also contributed to constitutive GPR183 internalization in a β-arrestin–independent manner, suggesting the existence of different pools of surface-localized GPR183. Chemotaxis mediated by GPR183 depended on receptor desensitization by β-arrestins but could be uncoupled from internalization, highlighting an important biological role for the recruitment of β-arrestin to GPR183. The role of distinct pathways in internalization and chemotaxis may aid in the development of GPR183-targeting drugs for specific disease contexts.

AB - The chemotactic G protein–coupled receptor GPR183 and its most potent endogenous oxysterol ligand 7α,25-dihydroxycholesterol (7α,25-OHC) are important for immune cell positioning in secondary lymphoid tissues. This receptor-ligand pair is associated with various diseases, in some cases contributing favorably and in other cases adversely, making GPR183 an attractive target for therapeutic intervention. We investigated the mechanisms underlying GPR183 internalization and the role of internalization in the main biological function of the receptor, chemotaxis. We found that the C terminus of the receptor was important for ligand-induced internalization but less so for constitutive (ligand-independent) internalization. β-arrestin potentiated ligand-induced internalization but was not required for ligand-induced or constitutive internalization. Caveolin and dynamin were the main mediators of both constitutive and ligand-induced receptor internalization in a mechanism independent of G protein activation. Clathrin-mediated endocytosis also contributed to constitutive GPR183 internalization in a β-arrestin–independent manner, suggesting the existence of different pools of surface-localized GPR183. Chemotaxis mediated by GPR183 depended on receptor desensitization by β-arrestins but could be uncoupled from internalization, highlighting an important biological role for the recruitment of β-arrestin to GPR183. The role of distinct pathways in internalization and chemotaxis may aid in the development of GPR183-targeting drugs for specific disease contexts.

U2 - 10.1126/scisignal.abl4283

DO - 10.1126/scisignal.abl4283

M3 - Journal article

C2 - 37014928

VL - 16

JO - Science Signaling

JF - Science Signaling

SN - 1945-0877

IS - 779

M1 - eabl4283

ER -

ID: 341483551