Anne Bormann, Marek B Körner, Anne-Kristin Dahse, Marie S Gläser, Johanna Irmer, Vera Lede, Judith Alenfelder, Joris Lehmann, Daniella C N Hall, Michael Thane, Michael Schleyer, Evi Kostenis, Torsten Schöneberg, Marina Bigl, Tobias Langenhan, Dmitrij Ljaschenko, Nicole Scholz
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引用次数: 0
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 Gαo-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.
期刊介绍:
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