New functions and signaling mechanisms for the class of adhesion G protein-coupled receptors

Abstract

The class of adhesion G protein–coupled receptors (aGPCRs), with 33 human homologs, is the second largest family of GPCRs. In addition to a seven‐transmembrane α‐helix—a structural feature of all GPCRs—the class of aGPCRs is characterized by the presence of a large N‐terminal extracellular region. In addition, all aGPCRs but one (GPR123) contain a GPCR autoproteolysis–inducing (GAIN) domain that mediates autoproteolytic cleavage at the GPCR autoproteolysis site motif to generate N‐ and a C‐terminal fragments (NTF and CTF, respectively) during protein maturation. Subsequently, the NTF and CTF are associated noncovalently as a heterodimer at the plasma membrane. While the biological function of the GAIN domain–mediated autocleavage is not fully understood, mounting evidence suggests that the NTF and CTF possess distinct biological activities in addition to their function as a receptor unit. We discuss recent advances in understanding the biological functions, signaling mechanisms, and disease associations of the aGPCRs.

Autoren

Ines Liebscher
Brian Ackley
Demet Araç
Donna M Ariestanti
Gabriela Aust
Byoung‐il Bae
Bigyan R Bista
James P Bridges
Joseph G Duman
Felix B Engel
Stefanie Giera
André M Goffinet
Randy A Hall
Jörg Hamann
Nicole Hartmann
Hsi‐Hsien Lin
Mingyao Liu
Rong Luo
Amit Mogha
Kelly R Monk
Miriam C Peeters
Simone Prömel
Susanne Ressl
Helgi B Schiöth
Séverine M Sigoillot
Helen Song
William S Talbot
Gregory G Tall
James P White
Uwe Wolfrum
Lei Xu
Xianhua Piao

DOI

10.1111/nyas.12580

eISSN

1749-6632

ISSN

0077-8923

Ausgabe der Veröffentlichung

1

Zeitschrift

Annals of the New York Academy of Sciences

Sprache

en

Online publication date

2014

Paginierung

43 - 64

Datum der Veröffentlichung

2014

Status

Published

Herausgeber

Wiley

Herausgeber URL

http://dx.doi.org/10.1111/nyas.12580

Datum der Datenerfassung

2023

Titel

New functions and signaling mechanisms for the class of adhesion G protein–coupled receptors

Ausgabe der Zeitschrift

1333

Data source: Crossref

Abstract

The class of adhesion G protein-coupled receptors (aGPCRs), with 33 human homologs, is the second largest family of GPCRs. In addition to a seven-transmembrane α-helix-a structural feature of all GPCRs-the class of aGPCRs is characterized by the presence of a large N-terminal extracellular region. In addition, all aGPCRs but one (GPR123) contain a GPCR autoproteolysis-inducing (GAIN) domain that mediates autoproteolytic cleavage at the GPCR autoproteolysis site motif to generate N- and a C-terminal fragments (NTF and CTF, respectively) during protein maturation. Subsequently, the NTF and CTF are associated noncovalently as a heterodimer at the plasma membrane. While the biological function of the GAIN domain-mediated autocleavage is not fully understood, mounting evidence suggests that the NTF and CTF possess distinct biological activities in addition to their function as a receptor unit. We discuss recent advances in understanding the biological functions, signaling mechanisms, and disease associations of the aGPCRs.

Addresses

Institute of Biochemistry, Molecular Biochemistry, Medical Faculty, University of Leipzig, Leipzig, Germany.

Autoren

Ines Liebscher
Brian Ackley
Demet Araç
Donna M Ariestanti
Gabriela Aust
Byoung-il Bae
Bigyan R Bista
James P Bridges
Joseph G Duman
Felix B Engel
Stefanie Giera
André M Goffinet
Randy A Hall
Jörg Hamann
Nicole Hartmann
Hsi-Hsien Lin
Mingyao Liu
Rong Luo
Amit Mogha
Kelly R Monk
Miriam C Peeters
Simone Prömel
Susanne Ressl
Helgi B Schiöth
Séverine M Sigoillot
Helen Song
William S Talbot
Gregory G Tall
James P White
Uwe Wolfrum
Lei Xu
Xianhua Piao

DOI

10.1111/nyas.12580

eISSN

1749-6632

Externe Identifier

PubMed Identifier: 25424900
PubMed Central ID: PMC4278406

Funding acknowledgements

NHGRI NIH HHS: T32 HG000044
NINDS NIH HHS: R01 NS057536
NINDS NIH HHS: R01 NS072394
National Institute of Neurological Disorders and Stroke: R01NS057536
NIGMS NIH HHS: R01 GM098591

Open access

false

ISSN

0077-8923

Zeitschrift

Annals of the New York Academy of Sciences

Schlüsselwörter

Synapses
Animals
Humans
Neoplasms
Receptors, G-Protein-Coupled
Developmental Disabilities
Cell Adhesion
Signal Transduction
Mutation

Sprache

eng

Medium

Print-Electronic

Online publication date

2014

Paginierung

43 - 64

Datum der Veröffentlichung

2014

Status

Published

Datum der Datenerfassung

2014

Titel

New functions and signaling mechanisms for the class of adhesion G protein-coupled receptors.

Sub types

Congress
Research Support, Non-U.S. Gov't
research-article

Ausgabe der Zeitschrift

1333

Data source: Europe PubMed Central

Abstract

The class of adhesion G protein-coupled receptors (aGPCRs), with 33 human homologs, is the second largest family of GPCRs. In addition to a seven-transmembrane α-helix-a structural feature of all GPCRs-the class of aGPCRs is characterized by the presence of a large N-terminal extracellular region. In addition, all aGPCRs but one (GPR123) contain a GPCR autoproteolysis-inducing (GAIN) domain that mediates autoproteolytic cleavage at the GPCR autoproteolysis site motif to generate N- and a C-terminal fragments (NTF and CTF, respectively) during protein maturation. Subsequently, the NTF and CTF are associated noncovalently as a heterodimer at the plasma membrane. While the biological function of the GAIN domain-mediated autocleavage is not fully understood, mounting evidence suggests that the NTF and CTF possess distinct biological activities in addition to their function as a receptor unit. We discuss recent advances in understanding the biological functions, signaling mechanisms, and disease associations of the aGPCRs.

Autoren

Ines Liebscher
Brian Ackley
Demet Araç
Donna M Ariestanti
Gabriela Aust
Byoung-il Bae
Bigyan R Bista
James P Bridges
Joseph G Duman
Felix B Engel
Stefanie Giera
André M Goffinet
Randy A Hall
Jörg Hamann
Nicole Hartmann
Hsi-Hsien Lin
Mingyao Liu
Rong Luo
Amit Mogha
Kelly R Monk
Miriam C Peeters
Simone Prömel
Susanne Ressl
Helgi B Schiöth
Séverine M Sigoillot
Helen Song
William S Talbot
Gregory G Tall
James P White
Uwe Wolfrum
Lei Xu
Xianhua Piao

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/25424900

DOI

10.1111/nyas.12580

eISSN

1749-6632

Externe Identifier

NIH Manuscript Submission ID: NIHMS638138
PubMed Central ID: PMC4278406

Funding acknowledgements

NIGMS NIH HHS: R01 GM098591
NINDS NIH HHS: R01 NS057536
NINDS NIH HHS: R01 NS072394
NHGRI NIH HHS: T32 HG000044

Ausgabe der Veröffentlichung

1

Zeitschrift

Ann N Y Acad Sci

Schlüsselwörter

adhesion G protein-coupled receptor
cancer
development
myelination
signal transduction
structural biology
synaptogenesis
Animals
Cell Adhesion
Developmental Disabilities
Humans
Mutation
Neoplasms
Receptors, G-Protein-Coupled
Signal Transduction
Synapses

Sprache

eng

Country

United States

Paginierung

43 - 64

Datum der Veröffentlichung

2014

Status

Published

Datum, an dem der Datensatz öffentlich gemacht wurde

2015

Titel

New functions and signaling mechanisms for the class of adhesion G protein-coupled receptors.

Sub types

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

Ausgabe der Zeitschrift

1333

Data source: PubMed

New functions and signaling mechanisms for the class of adhesion G protein-coupled receptors

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