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Ann N Y Acad Sci. 2019 Jun 6. doi: 10.1111/nyas.14094. [Epub ahead of print]

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

Author information

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

PMID:
31168816
DOI:
10.1111/nyas.14094

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