Intron retention of an adhesion GPCR generates 1TM isoforms required for 7TM-GPCR function

Adhesion G protein-coupled receptors (aGPCRs) are expressed in all organs and are involved in various mechanobiological processes. They are heavily alternatively spliced, forecasting an extraordinary molecular structural diversity. Here, we uncovered the existence of unconventional single-transmembrane (1TM)-containing ADGRL/Cirl proteins devoid of the conventional GPCR layout (i.e., the 7TM signaling unit) in Drosophila. These 1TM proteins are made as a result of intron retention and provide an N-terminal fragment that acts as an interactor to allow Gα<sub>o</sub>-dependent signaling through conventional 7TM-containing Cirl isoforms encoded by the same gene. This molecular mechanism determines sensory precision of neurons in response to mechanical stimulation in vivo. This action mode of aGPCR provides a promising entry point for experimental and therapeutic approaches to intervene in aGPCR signaling and implicates alternative splicing as a physiological strategy to express a given aGPCR together with its molecular interactor.

Authors

Institutions

Publication Details

Journal
Cell Reports
Published
2024-12-18
DOI
https://doi.org/10.1016/j.celrep.2024.115078
Citations
9
Primary Topic
Receptor Mechanisms and Signaling
Type
article
Field-Weighted Citation Impact
2.10

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Intron retention of an adhesion GPCR generates 1TM isoforms required for 7TM-GPCR function

Marek B. Körner, Joris Lehmann, Anne Bormann, Nicole Scholz et al.
9 citations
Cell Reports
Receptor Mechanisms and Signaling
2.10
article

Intron retention of an adhesion GPCR generates 1TM isoforms required for 7TM-GPCR function

Marek B. Körner, Joris Lehmann, Anne Bormann, Nicole Scholz, Judith Alenfelder, Vera Lede, Evi Kostenis, Tobias Langenhan, Daniella C. N. Hall, Anne-Kristin Dahse, Torsten Schöneberg, Dmitrij Ljaschenko, Michael Schleyer, Johanna Irmer, Michael Thane, Marina Bigl, Marie S. Gläser
article en
9 citations

Abstract

Adhesion G protein-coupled receptors (aGPCRs) are expressed in all organs and are involved in various mechanobiological processes. They are heavily alternatively spliced, forecasting an extraordinary molecular structural diversity. Here, we uncovered the existence of unconventional single-transmembrane (1TM)-containing ADGRL/Cirl proteins devoid of the conventional GPCR layout (i.e., the 7TM signaling unit) in Drosophila. These 1TM proteins are made as a result of intron retention and provide an N-terminal fragment that acts as an interactor to allow Gα<sub>o</sub>-dependent signaling through conventional 7TM-containing Cirl isoforms encoded by the same gene. This molecular mechanism determines sensory precision of neurons in response to mechanical stimulation in vivo. This action mode of aGPCR provides a promising entry point for experimental and therapeutic approaches to intervene in aGPCR signaling and implicates alternative splicing as a physiological strategy to express a given aGPCR together with its molecular interactor.

Cell ReportsVol. 44(1)
University of Bonn (DE), Martin Luther University Halle-Wittenberg (DE), Leipzig University (DE), Leibniz Institute for Neurobiology (DE)
Deutsche Forschungsgemeinschaft, Universität Leipzig, National Institutes of Health
Openalex Percentile: Top 12%
Receptor Mechanisms and Signaling
2.10
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.