14862
2015
eng
866-874
11
article
1
2017-05-17
--
--
The adhesion GPCR Latrophilin/CIRL shapes mechanosensation
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.
Cell Reports
10.1016/j.celrep.2015.04.008
urn:nbn:de:bvb:20-opus-148626
Cell Reports 2015, 11, 866-874. DOI: 10.1016/j.celrep.2015.04.008
CC BY-NC-ND: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell, Keine Bearbeitungen 4.0 International
Nicole Scholz
Jennifer Gehring
Chonglin Guan
Dmitrij Ljaschenko
Robin Fischer
Vetrivel Lakshmanan
Robert J. Kittel
Tobias Langenhan
eng
uncontrolled
\(\alpha\)-latrotoxin
eng
uncontrolled
chordotonal organs
eng
uncontrolled
Johnstons organ
eng
uncontrolled
ligand CD55
eng
uncontrolled
hearing
eng
uncontrolled
binding
eng
uncontrolled
shear stress
eng
uncontrolled
protein-coupled receptors
eng
uncontrolled
drosophila larvae
eng
uncontrolled
domain
Medizin und Gesundheit
open_access
Physiologisches Institut
Theodor-Boveri-Institut für Biowissenschaften
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/14862/032_Scholz_Cell_Reports.pdf
17052
2017
eng
e28360
6
article
1
2018-10-29
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--
Mechano-dependent signaling by Latrophilin/CIRL quenches cAMP in proprioceptive neurons
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.
eLife
10.7554/eLife.28360
urn:nbn:de:bvb:20-opus-170520
eLife 2017, 6:e28360. DOI: 10.7554/eLife.28360
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Nicole Scholz
Chonglin Guan
Matthias Nieberler
Alexander Grotmeyer
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
eng
uncontrolled
Latrophilin
eng
uncontrolled
adhesion GPCR
eng
uncontrolled
dCIRL
eng
uncontrolled
sensory physiology
eng
uncontrolled
metabotropic signalling
eng
uncontrolled
mechanotransduction
Medizin und Gesundheit
open_access
Institut für Pharmakologie und Toxikologie
Institut für Anatomie und Zellbiologie
Physiologisches Institut
Theodor-Boveri-Institut für Biowissenschaften
Rudolf-Virchow-Zentrum
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/17052/044_Scholz_ELIFE.pdf