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Heterogeneity in the processing defect of SLC26A4 mutants.

DC FieldValueLanguage
dc.contributor.author이민구-
dc.contributor.author이원상-
dc.contributor.author김경환-
dc.contributor.author윤재석-
dc.date.accessioned2015-05-19T17:41:30Z-
dc.date.available2015-05-19T17:41:30Z-
dc.date.issued2008-
dc.identifier.issn0022-2593-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/108631-
dc.description.abstractBACKGROUND: Mutations in the SLC26A4 gene are responsible for Pendred syndrome and non-syndromic hearing loss (DFNB4). This study analysed non-synonymous SLC26A4 mutations newly identified in East Asians, as well as three common mutations in Caucasians, to characterise their molecular pathogenic mechanisms and to explore the possibility of rescuing their processing defects. METHODS: A total of 11 non-synonymous disease associated mutations were generated and their effects on protein processing and on ion transporting activities were examined. RESULTS: Most of the mutations caused retention of the SLC26A4 gene product (pendrin) in the intracellular region, while wild-type pendrin reached the plasma membrane. Accordingly, these mutations abolished complex glycosylation and Cl(-)/HCO(3)(-) exchange activities of pendrin. However, significant heterogeneity in the processing of mutant pendrin molecules was observed. Each mutant protein exhibited a different cellular localisation, a different degree of N-glycosylation, and a different degree of sensitivity to the treatments that rescue processing defects. For example, H723R-pendrin, the most common mutation in East Asians, was mostly expressed in endoplasmic reticulum (ER), and its defects in protein processing and ion transporting activities were restored considerably by low temperature incubation. On the other hand, L236P-pendrin, the most common mutation in Caucasians, was mainly in the centrosomal region and was temperature insensitive. CONCLUSION: These results indicate that the processing of pendrin mutant protein is determined by mutant specific mechanisms, and that a mutant specific method would be required to rescue the conformational defects of each folding mutant-
dc.description.statementOfResponsibilityopen-
dc.format.extent411~419-
dc.relation.isPartOfJOURNAL OF MEDICAL GENETICS-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHChloride-Bicarbonate Antiporters/metabolism-
dc.subject.MESHDNA, Complementary/chemistry-
dc.subject.MESHDNA, Complementary/genetics-
dc.subject.MESHGenetic Variation-
dc.subject.MESHHeLa Cells-
dc.subject.MESHHearing Loss, Sensorineural/genetics*-
dc.subject.MESHHumans-
dc.subject.MESHHydrogen-Ion Concentration-
dc.subject.MESHImmunoblotting-
dc.subject.MESHMembrane Transport Proteins/biosynthesis-
dc.subject.MESHMembrane Transport Proteins/genetics*-
dc.subject.MESHMembrane Transport Proteins/metabolism-
dc.subject.MESHMutagenesis, Site-Directed-
dc.subject.MESHMutation-
dc.subject.MESHPolymerase Chain Reaction-
dc.subject.MESHSulfate Transporters-
dc.subject.MESHTransfection-
dc.titleHeterogeneity in the processing defect of SLC26A4 mutants.-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Pharmacology (약리학)-
dc.contributor.googleauthorJ S Yoon-
dc.contributor.googleauthorH-J Park-
dc.contributor.googleauthorS-Y Yoo-
dc.contributor.googleauthorW Namkung-
dc.contributor.googleauthorM J Jo-
dc.contributor.googleauthorS K Koo-
dc.contributor.googleauthorH-Y Park-
dc.contributor.googleauthorW-S Lee-
dc.contributor.googleauthorK H Kim-
dc.contributor.googleauthorM G Lee-
dc.identifier.doi10.1136/jmg.2007.054635-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA02781-
dc.contributor.localIdA03000-
dc.contributor.localIdA00311-
dc.contributor.localIdA02591-
dc.relation.journalcodeJ01582-
dc.identifier.eissn1468-6244-
dc.identifier.pmid18310264-
dc.identifier.urlhttp://jmg.bmj.com/content/45/7/411.long-
dc.subject.keywordChloride-Bicarbonate Antiporters/metabolism-
dc.subject.keywordDNA, Complementary/chemistry-
dc.subject.keywordDNA, Complementary/genetics-
dc.subject.keywordGenetic Variation-
dc.subject.keywordHeLa Cells-
dc.subject.keywordHearing Loss, Sensorineural/genetics*-
dc.subject.keywordHumans-
dc.subject.keywordHydrogen-Ion Concentration-
dc.subject.keywordImmunoblotting-
dc.subject.keywordMembrane Transport Proteins/biosynthesis-
dc.subject.keywordMembrane Transport Proteins/genetics*-
dc.subject.keywordMembrane Transport Proteins/metabolism-
dc.subject.keywordMutagenesis, Site-Directed-
dc.subject.keywordMutation-
dc.subject.keywordPolymerase Chain Reaction-
dc.subject.keywordSulfate Transporters-
dc.subject.keywordTransfection-
dc.contributor.alternativeNameLee, Min Goo-
dc.contributor.alternativeNameLee, Won Sang-
dc.contributor.alternativeNameKim, Kyung Hwan-
dc.contributor.alternativeNameYoon, Jae Seok-
dc.contributor.affiliatedAuthorLee, Min Goo-
dc.contributor.affiliatedAuthorLee, Won Sang-
dc.contributor.affiliatedAuthorKim, Kyung Hwan-
dc.contributor.affiliatedAuthorYoon, Jae Seok-
dc.rights.accessRightsnot free-
dc.citation.volume45-
dc.citation.number7-
dc.citation.startPage411-
dc.citation.endPage419-
dc.identifier.bibliographicCitationJOURNAL OF MEDICAL GENETICS, Vol.45(7) : 411-419, 2008-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers

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