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Mechano-dependent signaling by Latrophilin/CIRL quenches cAMP in proprioceptive neurons

Scholz, Nicole; Guan, Chonglin; Nieberler, Matthias; Grotemeyer, Alexander; Maiellaro, Isabella; Gao, Shiqiang; Beck, Sebastian; Pawlak, Matthias; Sauer, Markus; Asan, Esther; Rothemund, Sven; Winkler, Jana; Pr�mel, Simone; Nagel, Georg; Langenhan, Tobias; Kittel, Robert J.

Mechano-dependent signaling by Latrophilin/CIRL quenches cAMP in proprioceptive neurons Thumbnail


Authors

Nicole Scholz

Chonglin Guan

Matthias Nieberler

Alexander Grotemeyer

Shiqiang Gao

Sebastian Beck

Matthias Pawlak

Markus Sauer

Esther Asan

Sven Rothemund

Jana Winkler

Simone Pr�mel

Georg Nagel

Tobias Langenhan

Robert J. Kittel



Contributors

Nicole Scholz

Chonglin Guan

Matthias Nieberler

Alexander Grotemeyer

Shiqiang Gao

Sebastian Beck

Matthias Pawlak

Markus Sauer

Esther Asan

Sven Rothemund

Jana Winkler

Simone Pr�mel

Georg Nagel

Tobias Langenhan

Robert J. Kittel
Researcher

Abstract

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.

Journal Article Type Article
Acceptance Date Jun 29, 2017
Online Publication Date Aug 8, 2017
Publication Date Aug 8, 2017
Deposit Date Apr 8, 2020
Publicly Available Date May 20, 2020
Journal eLife
Electronic ISSN 2050-084X
Publisher eLife Sciences Publications
Peer Reviewed Peer Reviewed
Volume 6
Article Number e28360
DOI https://doi.org/10.7554/elife.28360
Public URL https://nottingham-repository.worktribe.com/output/4236911
Publisher URL https://elifesciences.org/articles/28360

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