![]() However, while elemental signaling properties of aGPCRs have recently become available ( Hamann et al., 2015), a molecular model of their signal transduction strategy is at large.īy combining genomic engineering with electrophysiological recordings, super-resolution microscopy and optogenetics, we have determined the critical steps that are required to transduce a mechanical stimulus into an intracellular response by an individual aGPCR, Drosophila Latrophilin/dCIRL. These examples collectively suggest that processing of mechanical stimuli may be a common feature of this receptor family ( Langenhan et al., 2016). Several aGPCRs have recently been linked to mechanosensitive functions ( Petersen et al., 2015 Scholz et al., 2015 White et al., 2014). Remarkably, as opposed to the majority of GPCRs, aGPCRs interact through their N-termini with membrane-tethered or ECM-fixed partner molecules rather than soluble compounds indicating that their function requires positional fixation outside the receptor-bearing cell ( Langenhan et al., 2013). G protein-coupled receptors (GPCRs) hand over stimulus-induced conformational changes to metabotropic signaling outlets that carry the signal to intracellular destinations.Īdhesion-type G protein-coupled receptors (aGPCRs) display structural characteristics that distinguish them as a separate family within the GPCR superfamily ( Hamann et al., 2015). However, our understanding of the underlying molecular mechanisms is far from complete. Sensory strategies for the perception of mechanical cues are essential for survival. 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. Intracellularly, dCIRL quenches cAMP levels upon mechanical activation thereby specifically increasing the mechanosensitivity of neurons. 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. ![]() Here we show that the Drosophila aGPCR Latrophilin/dCIRL acts in mechanosensory neurons by modulating ionotropic receptor currents, the initiating step of cellular mechanosensation. aGPCRs have been suggested to possess mechanosensory properties, though their mechanism of action is fully unknown. Correspondingly, this receptor family is linked to a multitude of diverse human diseases. 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.
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