TY  - JOUR
A1  - Scholz, Nicole
A1  - Gehring, Jennifer
A1  - Guan, Chonglin
A1  - Ljaschenko, Dmitrij
A1  - Fischer, Robin
A1  - Lakshmanan, Vetrivel
A1  - Kittel, Robert J.
A1  - Langenhan, Tobias
T1  - The adhesion GPCR Latrophilin/CIRL shapes mechanosensation
JF  - Cell Reports
N2  - G-protein-coupled receptors (GPCRs) are typically regarded as chemosensors that control cellular states in response to soluble extracellular cues. However, the modality of stimuli recognized through adhesion GPCR (aGPCR), the second largest class of the GPCR superfamily, is unresolved. Our study characterizes the Drosophila aGPCR Latrophilin/dCirl, a prototype member of this enigmatic receptor class. We show that dCirl shapes the perception of tactile, proprioceptive, and auditory stimuli through chordotonal neurons, the principal mechanosensors of Drosophila. dCirl sensitizes these neurons for the detection of mechanical stimulation by amplifying their input-output function. Our results indicate that aGPCR may generally process and modulate the perception of mechanical signals, linking these important stimuli to the sensory canon of the GPCR superfamily.
KW  - \(\alpha\)-latrotoxin
KW  - chordotonal organs
KW  - Johnstons organ
KW  - ligand CD55
KW  - hearing
KW  - binding
KW  - shear stress
KW  - protein-coupled receptors
KW  - drosophila larvae
KW  - domain
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148626
VL  - 11
ER  - 
TY  - JOUR
A1  - Scholz, Nicole
A1  - Guan, Chonglin
A1  - Nieberler, Matthias
A1  - Grotmeyer, Alexander
A1  - Maiellaro, Isabella
A1  - Gao, Shiqiang
A1  - Beck, Sebastian
A1  - Pawlak, Matthias
A1  - Sauer, Markus
A1  - Asan, Esther
A1  - Rothemund, Sven
A1  - Winkler, Jana
A1  - Prömel, Simone
A1  - Nagel, Georg
A1  - Langenhan, Tobias
A1  - Kittel, Robert J
T1  - Mechano-dependent signaling by Latrophilin/CIRL quenches cAMP in proprioceptive neurons
JF  - eLife
N2  - 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.
KW  - Latrophilin
KW  - adhesion GPCR
KW  - dCIRL
KW  - sensory physiology
KW  - metabotropic signalling
KW  - mechanotransduction
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170520
VL  - 6
IS  - e28360
ER  -