G12/13 is activated by acute tethered agonist exposure in the adhesion GPCR ADGRL3
| Autor: | Signe, Mathiasen, Tiago, Palmisano, Nicole A, Perry, Hannah M, Stoveken, Alex, Vizurraga, Dyke P, McEwen, Najeah, Okashah, Tobias, Langenhan, Asuka, Inoue, Nevin A, Lambert, Gregory G, Tall, Jonathan A, Javitch |
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| Rok vydání: | 2019 |
| Předmět: |
Mitogen-Activated Protein Kinase 1
Arrestin Mitogen-Activated Protein Kinase 3 Receptors Peptide Gene Expression GTP-Binding Protein alpha Subunits G12-G13 Recombinant Proteins Activating Transcription Factor 6 Receptors G-Protein-Coupled Kinetics Mice HEK293 Cells Animals GTP-Binding Protein alpha Subunits Gq-G11 Humans CRISPR-Cas Systems Peptides Cell Engineering Protein Binding Signal Transduction |
| Zdroj: | Nature chemical biology. 16(12) |
| ISSN: | 1552-4469 |
| Popis: | 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. Gα |
| Databáze: | OpenAIRE |
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