Mechano-dependent signaling by Latrophilin/CIRL quenches cAMP in proprioceptive neurons.
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 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.
['Scholz|Nicole|N|', 'Guan|Chonglin|C|', 'Nieberler|Matthias|M|', 'Grotemeyer|Alexander|A|', 'Maiellaro|Isabella|I|', 'Gao|Shiqiang|S|', 'Beck|Sebastian|S|', 'Pawlak|Matthias|M|', 'Sauer|Markus|M|', 'Asan|Esther|E|', 'Rothemund|Sven|S|', 'Winkler|Jana|J|', 'Prömel|Simone|S|', 'Nagel|Georg|G|', 'Langenhan|Tobias|T|0000-0002-9061-3809', 'Kittel|Robert J|RJ|0000-0002-9199-4826']
D000200:Action Potentials D000818:Animals D000242:Cyclic AMP D004330:Drosophila D029721:Drosophila Proteins D055724:Electrophysiological Phenomena D008465:Mechanoreceptors D061848:Optical Imaging D018000:Receptors, Peptide D011984:Sensory Receptor Cells
Latrophilin dCIRL D. melanogaster adhesion GPCR mechanotransduction metabotropic signalling neuroscience sensory physiology