The expanding functional roles and signaling mechanisms of adhesion G protein-coupled receptors

Rory K Morgan; Garret R Anderson; Demet Araç; Gabriela Aust; Nariman Balenga; Antony Boucard; James P Bridges; Felix B Engel; Caroline J Formstone; Maike D Glitsch; Ryan S Gray; Randy A Hall; Cheng-Chih Hsiao; Hee-Yong Kim; Alexander B Knierim; Deva Krupakar Kusuluri; Katherine Leon; Ines Liebscher; Xianhua Piao; Simone Prömel; Nicole Scholz; Swati Srivastava; Doreen Thor; Kimberley F Tolias; Yuri A Ushkaryov; Mario Vallon; Erwin G Van Meir; Benoit Vanhollebeke; Uwe Wolfrum; Kevin M Wright; Kelly R Monk; Amit Mogha

doi:10.1111/nyas.14094

The expanding functional roles and signaling mechanisms of adhesion G protein-coupled receptors

Ann N Y Acad Sci. 2019 Nov;1456(1):5-25. doi: 10.1111/nyas.14094. Epub 2019 Jun 6.

Authors

Rory K Morgan¹, Garret R Anderson², Demet Araç³, Gabriela Aust⁴, Nariman Balenga^{5

6}, Antony Boucard⁷, James P Bridges^{8

9}, Felix B Engel¹⁰, Caroline J Formstone^{11

12}, Maike D Glitsch¹³, Ryan S Gray¹⁴, Randy A Hall¹⁵, Cheng-Chih Hsiao¹⁶, Hee-Yong Kim¹⁷, Alexander B Knierim¹⁸, Deva Krupakar Kusuluri¹⁹, Katherine Leon³, Ines Liebscher¹⁸, Xianhua Piao²⁰, Simone Prömel¹⁸, Nicole Scholz²¹, Swati Srivastava¹⁰, Doreen Thor¹⁸, Kimberley F Tolias²², Yuri A Ushkaryov²³, Mario Vallon²⁴, Erwin G Van Meir²⁵, Benoit Vanhollebeke^{26

27}, Uwe Wolfrum¹⁹, Kevin M Wright¹, Kelly R Monk¹, Amit Mogha¹

Affiliations

¹ Vollum Institute, Oregon Health & Science University, Portland, Oregon.
² Department of Molecular, Cell and Systems Biology, University of California - Riverside, Riverside, California.
³ Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, Illinois.
⁴ Research Laboratories, Department of Surgery, Leipzig University, Leipzig, Germany.
⁵ Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland.
⁶ Program in Molecular and Structural Biology, Marlene and Stewart Greenebaum NCI Comprehensive Cancer Center, Baltimore, Maryland.
⁷ Department of Cell Biology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Mexico City, México.
⁸ Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati, Ohio.
⁹ Perinatal Institute, Section of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
¹⁰ Experimental Renal and Cardiovascular Research, Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
¹¹ Centre for Developmental Neurobiology, Guys Campus, Kings College London, London, UK.
¹² Department of Biological and Environmental Sciences, College Lane Campus, University of Hertfordshire, Hatfield, UK.
¹³ Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
¹⁴ Department of Pediatrics, University of Texas at Austin, Dell Medical School, Austin, Texas.
¹⁵ Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia.
¹⁶ Department of Experimental Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
¹⁷ Laboratory of Molecular Signaling, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland.
¹⁸ Rudolf Schönheimer Institute of Biochemistry, Molecular Biochemistry, Medical Faculty, Leipzig University, Leipzig, Germany.
¹⁹ Institute of Molecular Physiology, Johannes Gutenberg University of Mainz, Mainz, Germany.
²⁰ Newborn Brain Research Institute, Department of Pediatrics, University of California - San Francisco, San Francisco, California.
²¹ Rudolf Schönheimer Institute of Biochemistry, Division of General Biochemistry, Leipzig University, Leipzig, Germany.
²² Department of Neuroscience, Baylor College of Medicine, Houston, Texas.
²³ School of Pharmacy, University of Kent, Chatham, UK.
²⁴ Division of Hematology, Department of Medicine, Stanford University, Stanford, California.
²⁵ Laboratory of Molecular Neuro-Oncology, Departments of Neurosurgery and Hematology & Medical Oncology, School of Medicine and Winship Cancer Institute, Emory University, Atlanta, Georgia.
²⁶ Laboratory of Neurovascular Signaling, Department of Molecular Biology, ULB Neuroscience Institute, Université libre de Bruxelles (ULB), Gosselies, Belgium.
²⁷ Walloon Excellence in Life Sciences and Biotechnology (WELBIO), Wallonia, Belgium.

Abstract

The adhesion class of G protein-coupled receptors (GPCRs) is the second largest family of GPCRs (33 members in humans). Adhesion GPCRs (aGPCRs) are defined by a large extracellular N-terminal region that is linked to a C-terminal seven transmembrane (7TM) domain via a GPCR-autoproteolysis inducing (GAIN) domain containing a GPCR proteolytic site (GPS). Most aGPCRs undergo autoproteolysis at the GPS motif, but the cleaved fragments stay closely associated, with the N-terminal fragment (NTF) bound to the 7TM of the C-terminal fragment (CTF). The NTFs of most aGPCRs contain domains known to be involved in cell-cell adhesion, while the CTFs are involved in classical G protein signaling, as well as other intracellular signaling. In this workshop report, we review the most recent findings on the biology, signaling mechanisms, and physiological functions of aGPCRs.

Keywords: adhesion G protein-coupled receptor; cancer; development; immunology; mechanosensation; neurobiology; signal transduction; structural biology.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Humans
Receptors, G-Protein-Coupled / chemistry
Receptors, G-Protein-Coupled / metabolism*
Signal Transduction*

Substances

Receptors, G-Protein-Coupled

Abstract

Publication types

MeSH terms

Substances

Grants and funding