The Adhesion GPCR Latrophilin/CIRL Shapes Mechanosensation

•Latrophilin/CIRL is required for mechanosensory neuron function•Latrophilin/CIRL modulates sensitivity of neuronal mechanosensation•Latrophilin/CIRL interacts with TRP channels•In vivo role for a GPCR in mechanosensation is demonstrated

SummaryG-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.

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