Mechano-dependent signaling by Latrophilin/CIRL quenches cAMP in proprioceptive neurons
Nicole Scholz,
Chonglin Guan,
Matthias Nieberler,
Alexander Grotemeyer,
Isabella Maiellaro,
Shiqiang Gao,
Sebastian Beck,
Matthias Pawlak,
Markus Sauer,
Esther Asan,
Sven Rothemund,
Jana Winkler,
Simone Prömel,
Georg Nagel,
Tobias Langenhan,
Robert J Kittel
Affiliations
Nicole Scholz
Department of Neurophysiology, Institute of Physiology, University of Würzburg, Würzburg, Germany; Rudolf Schönheimer Institute of Biochemistry, Division of General Biochemistry, Medical Faculty, Leipzig University, Leipzig, Germany
Chonglin Guan
Department of Neurophysiology, Institute of Physiology, University of Würzburg, Würzburg, Germany
Matthias Nieberler
Department of Neurophysiology, Institute of Physiology, University of Würzburg, Würzburg, Germany
Alexander Grotemeyer
Department of Neurophysiology, Institute of Physiology, University of Würzburg, Würzburg, Germany
Isabella Maiellaro
Institute of Pharmacology and Toxicology, University of Würzburg, Würzburg, Germany; Rudolf Virchow Center, DFG-Research Center for Experimental Biomedicine, University of Würzburg, Würzburg, Germany
Shiqiang Gao
Department of Biology, Institute for Molecular Plant Physiology and Biophysics, University of Würzburg Biocenter, Würzburg, Germany
Sebastian Beck
Department of Biology, Institute for Molecular Plant Physiology and Biophysics, University of Würzburg Biocenter, Würzburg, Germany
Matthias Pawlak
Department of Neurophysiology, Institute of Physiology, University of Würzburg, Würzburg, Germany
Markus Sauer
Department of Biotechnology and Biophysics, University of Würzburg Biocenter, Würzburg, Germany
Esther Asan
Institute of Anatomy and Cell Biology, University of Würzburg, Würzburg, Germany
Sven Rothemund
Core Unit Peptide Technologies, Medical Faculty, Leipzig University, Leipzig, Germany
Jana Winkler
Rudolf Schönheimer Institute of Biochemistry, Division of Molecular Biochemistry, Medical Faculty, Leipzig University, Leipzig, Germany
Simone Prömel
Rudolf Schönheimer Institute of Biochemistry, Division of Molecular Biochemistry, Medical Faculty, Leipzig University, Leipzig, Germany
Georg Nagel
Department of Biology, Institute for Molecular Plant Physiology and Biophysics, University of Würzburg Biocenter, Würzburg, Germany
Department of Neurophysiology, Institute of Physiology, University of Würzburg, Würzburg, Germany; Rudolf Schönheimer Institute of Biochemistry, Division of General Biochemistry, Medical Faculty, Leipzig University, Leipzig, Germany
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.
