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dc.contributor.authorLuo, Rong
dc.contributor.authorJin, Zhaohui
dc.contributor.authorDeng, Yiyu
dc.contributor.authorStrokes, Natalie
dc.contributor.authorPiao, Xianhua
dc.contributor.editorMei, Lin
dc.date.accessioned2012-10-26T16:29:35Z
dc.date.available2012-10-26T16:29:35Z
dc.date.issued2012-01-4en_US
dc.identifier.citationPLoS One. 2012 Jan 4; 7(1):e29818en_US
dc.identifier.issn1932-6203en_US
dc.identifier.pmid22238662en_US
dc.identifier.doi10.1371/journal.pone.0029818en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/693
dc.description.abstractGPR56 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.rightsLuo 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.subjectResearch Articleen_US
dc.subjectBiologyen_US
dc.subjectBiochemistryen_US
dc.subjectBiophysicsen_US
dc.subjectGeneticsen_US
dc.subjectMolecular Cell Biologyen_US
dc.subjectSignal Transductionen_US
dc.subjectSignaling in Cellular Processesen_US
dc.subjectNeuroscienceen_US
dc.subjectPhysicsen_US
dc.subjectBiophysicsen_US
dc.subject.meshAnimalsen_US
dc.subject.meshBase Sequenceen_US
dc.subject.meshBinding Sitesen_US
dc.subject.meshBrainen_US
dc.subject.meshCollagen Type IIIen_US
dc.subject.meshHEK293 Cellsen_US
dc.subject.meshHumansen_US
dc.subject.meshMalformations of Cortical Developmenten_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Inbred BALB Cen_US
dc.subject.meshMice, Knockouten_US
dc.subject.meshModels, Biologicalen_US
dc.subject.meshModels, Molecularen_US
dc.subject.meshMolecular Sequence Dataen_US
dc.subject.meshMutationen_US
dc.subject.meshProtein Bindingen_US
dc.subject.meshProtein Interaction Domains and Motifsen_US
dc.subject.meshReceptors, G-Protein-Coupleden_US
dc.titleDisease-Associated Mutations Prevent GPR56-Collagen III Interactionen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC3251603en_US
dc.contributor.corporatenameDepartment of Neurology
refterms.dateFOA2019-04-10T00:33:20Z
html.description.abstractGPR56 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.


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