Cargando…

Mechanism for Adhesion G Protein-Coupled Receptor GPR56-Mediated RhoA Activation Induced By Collagen III Stimulation

GPR56 is a member of the adhesion G protein-coupled receptor (GPCR) family. Despite the importance of GPR56 in brain development, where mutations cause a devastating human brain malformation called bilateral frontoparietal polymicrogyria (BFPP), the signaling mechanism(s) remain largely unknown. Lik...

Descripción completa

Detalles Bibliográficos
Autores principales: Luo, Rong, Jeong, Sung-Jin, Yang, Annie, Wen, Miaoyun, Saslowsky, David E., Lencer, Wayne I., Araç, Demet, Piao, Xianhua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4065004/
https://www.ncbi.nlm.nih.gov/pubmed/24949629
http://dx.doi.org/10.1371/journal.pone.0100043
_version_ 1782322012171010048
author Luo, Rong
Jeong, Sung-Jin
Yang, Annie
Wen, Miaoyun
Saslowsky, David E.
Lencer, Wayne I.
Araç, Demet
Piao, Xianhua
author_facet Luo, Rong
Jeong, Sung-Jin
Yang, Annie
Wen, Miaoyun
Saslowsky, David E.
Lencer, Wayne I.
Araç, Demet
Piao, Xianhua
author_sort Luo, Rong
collection PubMed
description GPR56 is a member of the adhesion G protein-coupled receptor (GPCR) family. Despite the importance of GPR56 in brain development, where mutations cause a devastating human brain malformation called bilateral frontoparietal polymicrogyria (BFPP), the signaling mechanism(s) remain largely unknown. Like many other adhesion GPCRs, GPR56 is cleaved via a GPCR autoproteolysis-inducing (GAIN) domain into N- and C-terminal fragments (GPR56(N) and GPR56(C)); however, the biological significance of this cleavage is elusive. Taking advantage of the recent identification of a GPR56 ligand and the presence of BFPP-associated mutations, we investigated the molecular mechanism of GPR56 signaling. We demonstrate that ligand binding releases GPR56(N) from the membrane-bound GPR56(C) and triggers the association of GPR56(C) with lipid rafts and RhoA activation. Furthermore, one of the BFPP-associated mutations, L640R, does not affect collagen III-induced lipid raft association of GPR56. Instead, it specifically abolishes collagen III-mediated RhoA activation. Together, these findings reveal a novel signaling mechanism that may apply to other members of the adhesion GPCR family.
format Online
Article
Text
id pubmed-4065004
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-40650042014-06-25 Mechanism for Adhesion G Protein-Coupled Receptor GPR56-Mediated RhoA Activation Induced By Collagen III Stimulation Luo, Rong Jeong, Sung-Jin Yang, Annie Wen, Miaoyun Saslowsky, David E. Lencer, Wayne I. Araç, Demet Piao, Xianhua PLoS One Research Article GPR56 is a member of the adhesion G protein-coupled receptor (GPCR) family. Despite the importance of GPR56 in brain development, where mutations cause a devastating human brain malformation called bilateral frontoparietal polymicrogyria (BFPP), the signaling mechanism(s) remain largely unknown. Like many other adhesion GPCRs, GPR56 is cleaved via a GPCR autoproteolysis-inducing (GAIN) domain into N- and C-terminal fragments (GPR56(N) and GPR56(C)); however, the biological significance of this cleavage is elusive. Taking advantage of the recent identification of a GPR56 ligand and the presence of BFPP-associated mutations, we investigated the molecular mechanism of GPR56 signaling. We demonstrate that ligand binding releases GPR56(N) from the membrane-bound GPR56(C) and triggers the association of GPR56(C) with lipid rafts and RhoA activation. Furthermore, one of the BFPP-associated mutations, L640R, does not affect collagen III-induced lipid raft association of GPR56. Instead, it specifically abolishes collagen III-mediated RhoA activation. Together, these findings reveal a novel signaling mechanism that may apply to other members of the adhesion GPCR family. Public Library of Science 2014-06-20 /pmc/articles/PMC4065004/ /pubmed/24949629 http://dx.doi.org/10.1371/journal.pone.0100043 Text en © 2014 Luo et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Luo, Rong
Jeong, Sung-Jin
Yang, Annie
Wen, Miaoyun
Saslowsky, David E.
Lencer, Wayne I.
Araç, Demet
Piao, Xianhua
Mechanism for Adhesion G Protein-Coupled Receptor GPR56-Mediated RhoA Activation Induced By Collagen III Stimulation
title Mechanism for Adhesion G Protein-Coupled Receptor GPR56-Mediated RhoA Activation Induced By Collagen III Stimulation
title_full Mechanism for Adhesion G Protein-Coupled Receptor GPR56-Mediated RhoA Activation Induced By Collagen III Stimulation
title_fullStr Mechanism for Adhesion G Protein-Coupled Receptor GPR56-Mediated RhoA Activation Induced By Collagen III Stimulation
title_full_unstemmed Mechanism for Adhesion G Protein-Coupled Receptor GPR56-Mediated RhoA Activation Induced By Collagen III Stimulation
title_short Mechanism for Adhesion G Protein-Coupled Receptor GPR56-Mediated RhoA Activation Induced By Collagen III Stimulation
title_sort mechanism for adhesion g protein-coupled receptor gpr56-mediated rhoa activation induced by collagen iii stimulation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4065004/
https://www.ncbi.nlm.nih.gov/pubmed/24949629
http://dx.doi.org/10.1371/journal.pone.0100043
work_keys_str_mv AT luorong mechanismforadhesiongproteincoupledreceptorgpr56mediatedrhoaactivationinducedbycollageniiistimulation
AT jeongsungjin mechanismforadhesiongproteincoupledreceptorgpr56mediatedrhoaactivationinducedbycollageniiistimulation
AT yangannie mechanismforadhesiongproteincoupledreceptorgpr56mediatedrhoaactivationinducedbycollageniiistimulation
AT wenmiaoyun mechanismforadhesiongproteincoupledreceptorgpr56mediatedrhoaactivationinducedbycollageniiistimulation
AT saslowskydavide mechanismforadhesiongproteincoupledreceptorgpr56mediatedrhoaactivationinducedbycollageniiistimulation
AT lencerwaynei mechanismforadhesiongproteincoupledreceptorgpr56mediatedrhoaactivationinducedbycollageniiistimulation
AT aracdemet mechanismforadhesiongproteincoupledreceptorgpr56mediatedrhoaactivationinducedbycollageniiistimulation
AT piaoxianhua mechanismforadhesiongproteincoupledreceptorgpr56mediatedrhoaactivationinducedbycollageniiistimulation