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Mechano-dependent signaling by Latrophilin/CIRL quenches cAMP in proprioceptive neurons

Please always quote using this URN: urn:nbn:de:bvb:20-opus-170520
  • Adhesion-type G protein-coupled receptors (aGPCRs), a large molecule family with over 30 members in humans, operate in organ development, brain function and govern immunological responses. Correspondingly, this receptor family is linked to a multitude of diverse human diseases. aGPCRs have been suggested to possess mechanosensory properties, though their mechanism of action is fully unknown. Here we show that the Drosophila aGPCR Latrophilin/dCIRL acts in mechanosensory neurons by modulating ionotropic receptor currents, the initiating step ofAdhesion-type G protein-coupled receptors (aGPCRs), a large molecule family with over 30 members in humans, operate in organ development, brain function and govern immunological responses. Correspondingly, this receptor family is linked to a multitude of diverse human diseases. aGPCRs have been suggested to possess mechanosensory properties, though their mechanism of action is fully unknown. Here we show that the Drosophila aGPCR Latrophilin/dCIRL acts in mechanosensory neurons by modulating ionotropic receptor currents, the initiating step of cellular mechanosensation. This process depends on the length of the extended ectodomain and the tethered agonist of the receptor, but not on its autoproteolysis, a characteristic biochemical feature of the aGPCR family. Intracellularly, dCIRL quenches cAMP levels upon mechanical activation thereby specifically increasing the mechanosensitivity of neurons. These results provide direct evidence that the aGPCR dCIRL acts as a molecular sensor and signal transducer that detects and converts mechanical stimuli into a metabotropic response.show moreshow less

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Metadaten
Author: Nicole Scholz, Chonglin Guan, Matthias Nieberler, Alexander Grotmeyer, Isabella Maiellaro, Shiqiang Gao, Sebastian Beck, Matthias Pawlak, Markus Sauer, Esther Asan, Sven Rothemund, Jana Winkler, Simone Prömel, Georg Nagel, Tobias LangenhanORCiD, Robert J KittelORCiD
URN:urn:nbn:de:bvb:20-opus-170520
Document Type:Journal article
Faculties:Medizinische Fakultät / Institut für Pharmakologie und Toxikologie
Medizinische Fakultät / Institut für Anatomie und Zellbiologie
Medizinische Fakultät / Physiologisches Institut
Fakultät für Biologie / Theodor-Boveri-Institut für Biowissenschaften
Fakultät für Biologie / Rudolf-Virchow-Zentrum
Language:English
Parent Title (English):eLife
Year of Completion:2017
Volume:6
Issue:e28360
Source:eLife 2017, 6:e28360. DOI: 10.7554/eLife.28360
DOI:https://doi.org/10.7554/eLife.28360
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:Latrophilin; adhesion GPCR; dCIRL; mechanotransduction; metabotropic signalling; sensory physiology
Release Date:2019/09/27
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International