File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Loss-of-function and residual channel activity of connexin26 mutations associated with non-syndromic deafness

TitleLoss-of-function and residual channel activity of connexin26 mutations associated with non-syndromic deafness
Authors
KeywordsChannel
Cochlea
Gap junction
Genetic disease
Xenopus
Issue Date2003
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/febslet
Citation
Febs Letters, 2003, v. 533 n. 1-3, p. 79-88 How to Cite?
AbstractConnexins are the protein subunits of gap junction channels that allow a direct signaling pathway between networks of cells. The specific role of connexin channels in the homeostasis of different organs has been validated by the association of mutations in several human connexins with a variety of genetic diseases. Several connexins are present in the mammalian cochlea and at least four of them have been proposed as genes causing sensorineural hearing loss. We have started our functional analysis by selecting nine mutations in Cx26 that are associated with non-syndromic recessive deafness (DFNB1). We have observed that both human Cx26 wild-type (HCx26wt) and the F83L polymorphism, found in unaffected controls, generated electrical conductance between paired Xenopus oocytes, which was several orders of magnitude greater than that measured in water-injected controls. In contrast, most recessive Cx26 mutations (identified in DFNB1 patients) resulted in a simple loss of channel activity. In addition, the V37I mutation, originally identified as a polymorphism in heterozygous unaffected individuals, was devoid of function and thus may be pathologically significant. Unexpectedly, we have found that the recessive mutation V84L retained functional activity in both paired Xenopus oocytes and transfected HeLa cells. Furthermore, both the magnitude of macroscopic junctional conductance and its voltage-gating properties were indistinguishable from those of HCx26wt. The identification of functional differences of disease causing mutations may lead to define which permeation or gating properties of Cx26 are necessary for normal auditory function in humans and will be instrumental in identifying the molecular steps leading to DFNB1. © 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.
Persistent Identifierhttp://hdl.handle.net/10722/132708
ISSN
2015 Impact Factor: 3.519
2015 SCImago Journal Rankings: 2.026
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorBruzzone, Ren_HK
dc.contributor.authorVeronesi, Ven_HK
dc.contributor.authorGomès, Den_HK
dc.contributor.authorBicego, Men_HK
dc.contributor.authorDuval, Nen_HK
dc.contributor.authorMarlin, Sen_HK
dc.contributor.authorPetit, Cen_HK
dc.contributor.authorD'Andrea, Pen_HK
dc.contributor.authorWhite, TWen_HK
dc.date.accessioned2011-03-28T09:28:26Z-
dc.date.available2011-03-28T09:28:26Z-
dc.date.issued2003en_HK
dc.identifier.citationFebs Letters, 2003, v. 533 n. 1-3, p. 79-88en_HK
dc.identifier.issn0014-5793en_HK
dc.identifier.urihttp://hdl.handle.net/10722/132708-
dc.description.abstractConnexins are the protein subunits of gap junction channels that allow a direct signaling pathway between networks of cells. The specific role of connexin channels in the homeostasis of different organs has been validated by the association of mutations in several human connexins with a variety of genetic diseases. Several connexins are present in the mammalian cochlea and at least four of them have been proposed as genes causing sensorineural hearing loss. We have started our functional analysis by selecting nine mutations in Cx26 that are associated with non-syndromic recessive deafness (DFNB1). We have observed that both human Cx26 wild-type (HCx26wt) and the F83L polymorphism, found in unaffected controls, generated electrical conductance between paired Xenopus oocytes, which was several orders of magnitude greater than that measured in water-injected controls. In contrast, most recessive Cx26 mutations (identified in DFNB1 patients) resulted in a simple loss of channel activity. In addition, the V37I mutation, originally identified as a polymorphism in heterozygous unaffected individuals, was devoid of function and thus may be pathologically significant. Unexpectedly, we have found that the recessive mutation V84L retained functional activity in both paired Xenopus oocytes and transfected HeLa cells. Furthermore, both the magnitude of macroscopic junctional conductance and its voltage-gating properties were indistinguishable from those of HCx26wt. The identification of functional differences of disease causing mutations may lead to define which permeation or gating properties of Cx26 are necessary for normal auditory function in humans and will be instrumental in identifying the molecular steps leading to DFNB1. © 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.en_HK
dc.languageengen_US
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/febsleten_HK
dc.relation.ispartofFEBS Lettersen_HK
dc.subjectChannelen_HK
dc.subjectCochleaen_HK
dc.subjectGap junctionen_HK
dc.subjectGenetic diseaseen_HK
dc.subjectXenopusen_HK
dc.titleLoss-of-function and residual channel activity of connexin26 mutations associated with non-syndromic deafnessen_HK
dc.typeArticleen_HK
dc.identifier.emailBruzzone, R: bruzzone@hkucc.hku.hken_HK
dc.identifier.authorityBruzzone, R=rp01442en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/S0014-5793(02)03755-9en_HK
dc.identifier.pmid12505163-
dc.identifier.scopuseid_2-s2.0-0037413825en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0037413825&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume533en_HK
dc.identifier.issue1-3en_HK
dc.identifier.spage79en_HK
dc.identifier.epage88en_HK
dc.identifier.isiWOS:000180260000015-
dc.publisher.placeNetherlandsen_HK
dc.identifier.scopusauthoridBruzzone, R=7006793327en_HK
dc.identifier.scopusauthoridVeronesi, V=6701534503en_HK
dc.identifier.scopusauthoridGomès, D=7005538633en_HK
dc.identifier.scopusauthoridBicego, M=7004711890en_HK
dc.identifier.scopusauthoridDuval, N=7003504203en_HK
dc.identifier.scopusauthoridMarlin, S=7003313482en_HK
dc.identifier.scopusauthoridPetit, C=7202973256en_HK
dc.identifier.scopusauthoridD'Andrea, P=7005979859en_HK
dc.identifier.scopusauthoridWhite, TW=35499703300en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats