Disease-Associated Mutations Prevent GPR56-Collagen III Interaction
dc.contributor.author | Luo, Rong | |
dc.contributor.author | Jin, Zhaohui | |
dc.contributor.author | Deng, Yiyu | |
dc.contributor.author | Strokes, Natalie | |
dc.contributor.author | Piao, Xianhua | |
dc.contributor.editor | Mei, Lin | |
dc.date.accessioned | 2012-10-26T16:29:35Z | |
dc.date.available | 2012-10-26T16:29:35Z | |
dc.date.issued | 2012-01-4 | en_US |
dc.identifier.citation | PLoS One. 2012 Jan 4; 7(1):e29818 | en_US |
dc.identifier.issn | 1932-6203 | en_US |
dc.identifier.pmid | 22238662 | en_US |
dc.identifier.doi | 10.1371/journal.pone.0029818 | en_US |
dc.identifier.uri | http://hdl.handle.net/10675.2/693 | |
dc.description.abstract | GPR56 is a member of the adhesion G protein-coupled receptor (GPCR) family. Mutations in GPR56 cause a devastating human brain malformation called bilateral frontoparietal polymicrogyria (BFPP). Using the N-terminal fragment of GPR56 (GPR56N) as a probe, we have recently demonstrated that collagen III is the ligand of GPR56 in the developing brain. In this report, we discover a new functional domain in GPR56N, the ligand binding domain. This domain contains four disease-associated mutations and two N-glycosylation sites. Our study reveals that although glycosylation is not required for ligand binding, each of the four disease-associated mutations completely abolish the ligand binding ability of GPR56. Our data indicates that these four single missense mutations cause BFPP mostly by abolishing the ability of GPR56 to bind to its ligand, collagen III, in addition to affecting GPR56 protein surface expression as previously shown. | |
dc.rights | Luo et al. 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 credited. | en_US |
dc.subject | Research Article | en_US |
dc.subject | Biology | en_US |
dc.subject | Biochemistry | en_US |
dc.subject | Biophysics | en_US |
dc.subject | Genetics | en_US |
dc.subject | Molecular Cell Biology | en_US |
dc.subject | Signal Transduction | en_US |
dc.subject | Signaling in Cellular Processes | en_US |
dc.subject | Neuroscience | en_US |
dc.subject | Physics | en_US |
dc.subject | Biophysics | en_US |
dc.subject.mesh | Animals | en_US |
dc.subject.mesh | Base Sequence | en_US |
dc.subject.mesh | Binding Sites | en_US |
dc.subject.mesh | Brain | en_US |
dc.subject.mesh | Collagen Type III | en_US |
dc.subject.mesh | HEK293 Cells | en_US |
dc.subject.mesh | Humans | en_US |
dc.subject.mesh | Malformations of Cortical Development | en_US |
dc.subject.mesh | Mice | en_US |
dc.subject.mesh | Mice, Inbred BALB C | en_US |
dc.subject.mesh | Mice, Knockout | en_US |
dc.subject.mesh | Models, Biological | en_US |
dc.subject.mesh | Models, Molecular | en_US |
dc.subject.mesh | Molecular Sequence Data | en_US |
dc.subject.mesh | Mutation | en_US |
dc.subject.mesh | Protein Binding | en_US |
dc.subject.mesh | Protein Interaction Domains and Motifs | en_US |
dc.subject.mesh | Receptors, G-Protein-Coupled | en_US |
dc.title | Disease-Associated Mutations Prevent GPR56-Collagen III Interaction | en_US |
dc.type | Article | en_US |
dc.identifier.pmcid | PMC3251603 | en_US |
dc.contributor.corporatename | Department of Neurology | |
refterms.dateFOA | 2019-04-10T00:33:20Z | |
html.description.abstract | GPR56 is a member of the adhesion G protein-coupled receptor (GPCR) family. Mutations in GPR56 cause a devastating human brain malformation called bilateral frontoparietal polymicrogyria (BFPP). Using the N-terminal fragment of GPR56 (GPR56N) as a probe, we have recently demonstrated that collagen III is the ligand of GPR56 in the developing brain. In this report, we discover a new functional domain in GPR56N, the ligand binding domain. This domain contains four disease-associated mutations and two N-glycosylation sites. Our study reveals that although glycosylation is not required for ligand binding, each of the four disease-associated mutations completely abolish the ligand binding ability of GPR56. Our data indicates that these four single missense mutations cause BFPP mostly by abolishing the ability of GPR56 to bind to its ligand, collagen III, in addition to affecting GPR56 protein surface expression as previously shown. |