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...
Autores principales: | , , , , , , , |
---|---|
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 |