title: The GPS motif is a molecular switch for bimodal activities of adhesion class G protein-coupled receptors.
abstract: Adhesion class G protein-coupled receptors (aGPCR) form the second largest group of seven-transmembrane-spanning (7TM) receptors whose molecular layout and function differ from canonical 7TM receptors. Despite their essential roles in immunity, tumorigenesis, and development, the mechanisms of aGPCR activation and signal transduction have remained obscure to date. Here, we use a transgenic assay to define the protein domains required in vivo for the activity of the prototypical aGPCR LAT-1/Latrophilin in Caenorhabditis elegans. We show that the GPCR proteolytic site (GPS) motif, the molecular hallmark feature of the entire aGPCR class, is essential for LAT-1 signaling serving in two different activity modes of the receptor. Surprisingly, neither mode requires cleavage but presence of the GPS, which relays interactions with at least two different partners. Our work thus uncovers the versatile nature of aGPCR activity in molecular detail and places the GPS motif in a central position for diverse protein-protein interactions.
authors.affiliation: Department of Biochemistry, University of Oxford, UK.
authors.forename: Simone
authors.initials: S
authors.lastname: Prömel
authors.forename: Marie
authors.initials: M
authors.lastname: Frickenhaus
authors.forename: Samantha
authors.initials: S
authors.lastname: Hughes
authors.forename: Lamia
authors.initials: L
authors.lastname: Mestek
authors.forename: David
authors.initials: D
authors.lastname: Staunton
authors.forename: Alison
authors.initials: A
authors.lastname: Woollard
authors.forename: Ioannis
authors.initials: I
authors.lastname: Vakonakis
authors.forename: Torsten
authors.initials: T
authors.lastname: Schöneberg
authors.forename: Ralf
authors.initials: R
authors.lastname: Schnabel
authors.forename: Andreas P
authors.initials: AP
authors.lastname: Russ
authors.forename: Tobias
authors.initials: T
authors.lastname: Langenhan
mesh_terms: D020816:Amino Acid Motifs / Q000502:physiology; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D018000:Receptors, Peptide / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D029742:Caenorhabditis elegans Proteins; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; C483879:lat-1 protein, C elegans