G12/13 is activated by acute tethered agonist exposure in the adhesion GPCR ADGRL3

Research output: Contribution to journalJournal articleResearchpeer-review

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G12/13 is activated by acute tethered agonist exposure in the adhesion GPCR ADGRL3. / Mathiasen, Signe; Palmisano, Tiago; Perry, Nicole A.; Stoveken, Hannah M.; Vizurraga, Alex; McEwen, Dyke P.; Okashah, Najeah; Langenhan, Tobias; Inoue, Asuka; Lambert, Nevin A.; Tall, Gregory G.; Javitch, Jonathan A.

In: Nature Chemical Biology, Vol. 16, No. 12, 12.2020, p. 1343–1350 .

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Mathiasen, S, Palmisano, T, Perry, NA, Stoveken, HM, Vizurraga, A, McEwen, DP, Okashah, N, Langenhan, T, Inoue, A, Lambert, NA, Tall, GG & Javitch, JA 2020, 'G12/13 is activated by acute tethered agonist exposure in the adhesion GPCR ADGRL3', Nature Chemical Biology, vol. 16, no. 12, pp. 1343–1350 . https://doi.org/10.1038/s41589-020-0617-7

APA

Mathiasen, S., Palmisano, T., Perry, N. A., Stoveken, H. M., Vizurraga, A., McEwen, D. P., Okashah, N., Langenhan, T., Inoue, A., Lambert, N. A., Tall, G. G., & Javitch, J. A. (2020). G12/13 is activated by acute tethered agonist exposure in the adhesion GPCR ADGRL3. Nature Chemical Biology, 16(12), 1343–1350 . https://doi.org/10.1038/s41589-020-0617-7

Vancouver

Mathiasen S, Palmisano T, Perry NA, Stoveken HM, Vizurraga A, McEwen DP et al. G12/13 is activated by acute tethered agonist exposure in the adhesion GPCR ADGRL3. Nature Chemical Biology. 2020 Dec;16(12):1343–1350 . https://doi.org/10.1038/s41589-020-0617-7

Author

Mathiasen, Signe ; Palmisano, Tiago ; Perry, Nicole A. ; Stoveken, Hannah M. ; Vizurraga, Alex ; McEwen, Dyke P. ; Okashah, Najeah ; Langenhan, Tobias ; Inoue, Asuka ; Lambert, Nevin A. ; Tall, Gregory G. ; Javitch, Jonathan A. / G12/13 is activated by acute tethered agonist exposure in the adhesion GPCR ADGRL3. In: Nature Chemical Biology. 2020 ; Vol. 16, No. 12. pp. 1343–1350 .

Bibtex

@article{ea90b754085c4418816507cf381ba25f,
title = "G12/13 is activated by acute tethered agonist exposure in the adhesion GPCR ADGRL3",
abstract = "The adhesion G-protein-coupled receptor (GPCR) latrophilin 3 (ADGRL3) has been associated with increased risk of attention deficit hyperactivity disorder (ADHD) and substance use in human genetic studies. Knockdown in multiple species leads to hyperlocomotion and altered dopamine signaling. Thus, ADGRL3 is a potential target for treatment of neuropsychiatric disorders that involve dopamine dysfunction, but its basic signaling properties are poorly understood. Identification of adhesion GPCR signaling partners has been limited by a lack of tools to acutely activate these receptors in living cells. Here, we design a novel acute activation strategy to characterize ADGRL3 signaling by engineering a receptor construct in which we could trigger acute activation enzymatically. Using this assay, we found that ADGRL3 signals through G12/G13 and Gq, with G12/13 the most robustly activated. G alpha(12/13) is a new player in ADGRL3 biology, opening up unexplored roles for ADGRL3 in the brain. Our methodological advancements should be broadly useful in adhesion GPCR research.",
keywords = "PROTEIN-COUPLED RECEPTORS, CELL-ADHESION, LATROPHILIN, GPR56, ADHD, IDENTIFICATION, FORSKOLIN, TERMINUS, LIGANDS, GPR126",
author = "Signe Mathiasen and Tiago Palmisano and Perry, {Nicole A.} and Stoveken, {Hannah M.} and Alex Vizurraga and McEwen, {Dyke P.} and Najeah Okashah and Tobias Langenhan and Asuka Inoue and Lambert, {Nevin A.} and Tall, {Gregory G.} and Javitch, {Jonathan A.}",
year = "2020",
month = dec,
doi = "10.1038/s41589-020-0617-7",
language = "English",
volume = "16",
pages = "1343–1350 ",
journal = "Nature Chemical Biology",
issn = "1552-4450",
publisher = "nature publishing group",
number = "12",

}

RIS

TY - JOUR

T1 - G12/13 is activated by acute tethered agonist exposure in the adhesion GPCR ADGRL3

AU - Mathiasen, Signe

AU - Palmisano, Tiago

AU - Perry, Nicole A.

AU - Stoveken, Hannah M.

AU - Vizurraga, Alex

AU - McEwen, Dyke P.

AU - Okashah, Najeah

AU - Langenhan, Tobias

AU - Inoue, Asuka

AU - Lambert, Nevin A.

AU - Tall, Gregory G.

AU - Javitch, Jonathan A.

PY - 2020/12

Y1 - 2020/12

N2 - The adhesion G-protein-coupled receptor (GPCR) latrophilin 3 (ADGRL3) has been associated with increased risk of attention deficit hyperactivity disorder (ADHD) and substance use in human genetic studies. Knockdown in multiple species leads to hyperlocomotion and altered dopamine signaling. Thus, ADGRL3 is a potential target for treatment of neuropsychiatric disorders that involve dopamine dysfunction, but its basic signaling properties are poorly understood. Identification of adhesion GPCR signaling partners has been limited by a lack of tools to acutely activate these receptors in living cells. Here, we design a novel acute activation strategy to characterize ADGRL3 signaling by engineering a receptor construct in which we could trigger acute activation enzymatically. Using this assay, we found that ADGRL3 signals through G12/G13 and Gq, with G12/13 the most robustly activated. G alpha(12/13) is a new player in ADGRL3 biology, opening up unexplored roles for ADGRL3 in the brain. Our methodological advancements should be broadly useful in adhesion GPCR research.

AB - The adhesion G-protein-coupled receptor (GPCR) latrophilin 3 (ADGRL3) has been associated with increased risk of attention deficit hyperactivity disorder (ADHD) and substance use in human genetic studies. Knockdown in multiple species leads to hyperlocomotion and altered dopamine signaling. Thus, ADGRL3 is a potential target for treatment of neuropsychiatric disorders that involve dopamine dysfunction, but its basic signaling properties are poorly understood. Identification of adhesion GPCR signaling partners has been limited by a lack of tools to acutely activate these receptors in living cells. Here, we design a novel acute activation strategy to characterize ADGRL3 signaling by engineering a receptor construct in which we could trigger acute activation enzymatically. Using this assay, we found that ADGRL3 signals through G12/G13 and Gq, with G12/13 the most robustly activated. G alpha(12/13) is a new player in ADGRL3 biology, opening up unexplored roles for ADGRL3 in the brain. Our methodological advancements should be broadly useful in adhesion GPCR research.

KW - PROTEIN-COUPLED RECEPTORS

KW - CELL-ADHESION

KW - LATROPHILIN

KW - GPR56

KW - ADHD

KW - IDENTIFICATION

KW - FORSKOLIN

KW - TERMINUS

KW - LIGANDS

KW - GPR126

U2 - 10.1038/s41589-020-0617-7

DO - 10.1038/s41589-020-0617-7

M3 - Journal article

VL - 16

SP - 1343

EP - 1350

JO - Nature Chemical Biology

JF - Nature Chemical Biology

SN - 1552-4450

IS - 12

ER -

ID: 311723150