The GPS Motif Is a Molecular Switch for Bimodal Activities of Adhesion Class G Protein-Coupled Receptors

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 aGPC...

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Main Authors:	Simone Prömel, Marie Frickenhaus, Samantha Hughes, Lamia Mestek, David Staunton, Alison Woollard, Ioannis Vakonakis, Torsten Schöneberg, Ralf Schnabel, Andreas P. Russ, Tobias Langenhan
Format:	Article
Language:	English
Published:	Elsevier 2012-08-01
Series:	Cell Reports
Online Access:	http://www.sciencedirect.com/science/article/pii/S2211124712001751

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spelling	doaj-d46d010d9fbc404a8102cca8d868f5162020-11-25T02:08:40ZengElsevierCell Reports2211-12472012-08-012232133110.1016/j.celrep.2012.06.015The GPS Motif Is a Molecular Switch for Bimodal Activities of Adhesion Class G Protein-Coupled ReceptorsSimone Prömel0Marie Frickenhaus1Samantha Hughes2Lamia Mestek3David Staunton4Alison Woollard5Ioannis Vakonakis6Torsten Schöneberg7Ralf Schnabel8Andreas P. Russ9Tobias Langenhan10Department of Biochemistry, University of Oxford, South Parks Road, OX1 3QU Oxford, UKDepartment of Biochemistry, University of Oxford, South Parks Road, OX1 3QU Oxford, UKDepartment of Biochemistry, University of Oxford, South Parks Road, OX1 3QU Oxford, UKDepartment of Biochemistry, University of Oxford, South Parks Road, OX1 3QU Oxford, UKDepartment of Biochemistry, University of Oxford, South Parks Road, OX1 3QU Oxford, UKDepartment of Biochemistry, University of Oxford, South Parks Road, OX1 3QU Oxford, UKDepartment of Biochemistry, University of Oxford, South Parks Road, OX1 3QU Oxford, UKInstitute of Biochemistry, Molecular Biochemistry, Medical Faculty, University of Leipzig, Johannisallee 30, 04103 Leipzig, GermanyInstitut für Genetik, TU Braunschweig, 38106 Braunschweig, GermanyDepartment of Biochemistry, University of Oxford, South Parks Road, OX1 3QU Oxford, UKDepartment of Biochemistry, University of Oxford, South Parks Road, OX1 3QU Oxford, UK 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. http://www.sciencedirect.com/science/article/pii/S2211124712001751
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Simone Prömel Marie Frickenhaus Samantha Hughes Lamia Mestek David Staunton Alison Woollard Ioannis Vakonakis Torsten Schöneberg Ralf Schnabel Andreas P. Russ Tobias Langenhan
spellingShingle	Simone Prömel Marie Frickenhaus Samantha Hughes Lamia Mestek David Staunton Alison Woollard Ioannis Vakonakis Torsten Schöneberg Ralf Schnabel Andreas P. Russ Tobias Langenhan The GPS Motif Is a Molecular Switch for Bimodal Activities of Adhesion Class G Protein-Coupled Receptors Cell Reports
author_facet	Simone Prömel Marie Frickenhaus Samantha Hughes Lamia Mestek David Staunton Alison Woollard Ioannis Vakonakis Torsten Schöneberg Ralf Schnabel Andreas P. Russ Tobias Langenhan
author_sort	Simone Prömel
title	The GPS Motif Is a Molecular Switch for Bimodal Activities of Adhesion Class G Protein-Coupled Receptors
title_short	The GPS Motif Is a Molecular Switch for Bimodal Activities of Adhesion Class G Protein-Coupled Receptors
title_full	The GPS Motif Is a Molecular Switch for Bimodal Activities of Adhesion Class G Protein-Coupled Receptors
title_fullStr	The GPS Motif Is a Molecular Switch for Bimodal Activities of Adhesion Class G Protein-Coupled Receptors
title_full_unstemmed	The GPS Motif Is a Molecular Switch for Bimodal Activities of Adhesion Class G Protein-Coupled Receptors
title_sort	gps motif is a molecular switch for bimodal activities of adhesion class g protein-coupled receptors
publisher	Elsevier
series	Cell Reports
issn	2211-1247
publishDate	2012-08-01
description	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.
url	http://www.sciencedirect.com/science/article/pii/S2211124712001751
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The GPS Motif Is a Molecular Switch for Bimodal Activities of Adhesion Class G Protein-Coupled Receptors

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