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Article: Connexin32 mutations associated with X-linked Charcot-Marie-Tooth disease show two distinct behaviors: Loss of function and altered gating properties

TitleConnexin32 mutations associated with X-linked Charcot-Marie-Tooth disease show two distinct behaviors: Loss of function and altered gating properties
Authors
KeywordsChannel
Gap junction
Myelin
Neuropathy
Peripheral nervous system
Schwann cell
Issue Date1998
PublisherSociety for Neuroscience. The Journal's web site is located at http://www.jneurosci.org
Citation
Journal Of Neuroscience, 1998, v. 18 n. 11, p. 4063-4075 How to Cite?
AbstractThe X-linked form of Charcot-Marie-Tooth disease (CMTX) is associated with mutations in the gene encoding connexin32 (Cx32), which is expressed in Schwann cells. We have compared the functional properties of 11 Cx32 mutations with those of the wild-type protein by testing their ability to form intercellular channels in the paired oocyte expression system. Although seven mutations were functionally incompetent, four others were able to generate intercellular currents of the same order of magnitude as those induced by wild-type Cx32 (Cx32wt). In homotypic oocyte pairs, CMTX mutations retaining functional activity induced the development of junctional currents that exhibited changes in the sensitivity and kinetics of voltage dependence with respect to that of Cx32wt. The four mutations were also capable of interacting in heterotypic configuration with the wild-type protein, and in one case the result was a marked rectification of junctional currents in response to voltage steps of opposite polarity. In addition, the functional CMTX mutations displayed the same selective pattern of compatibility as Cx32wt, interacting with Cx26, Cx46, and Cx50 but failing to do so with Cx40. Although the functional mutations exhibited sensitivity to cytoplasmic acidification, which induced a ≤80% decrease in junctional currents, both the rate and extent of channel closure were enhanced markedly for two of them. Together, these results indicate that the functional consequences of CMTX mutations of Cx32 are of two drastically distinct kinds. The presence of a functional group of mutations suggests that a selective deficit of Cx32 channels may be sufficient to impair the homeostasis of Schwann cells and lead to the development of CMTX.
Persistent Identifierhttp://hdl.handle.net/10722/132734
ISSN
2015 Impact Factor: 5.924
2015 SCImago Journal Rankings: 5.105
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorRessot, Cen_HK
dc.contributor.authorGomès, Den_HK
dc.contributor.authorDautigny, Aen_HK
dc.contributor.authorPhamDinh, Den_HK
dc.contributor.authorBruzzone, Ren_HK
dc.date.accessioned2011-03-28T09:28:39Z-
dc.date.available2011-03-28T09:28:39Z-
dc.date.issued1998en_HK
dc.identifier.citationJournal Of Neuroscience, 1998, v. 18 n. 11, p. 4063-4075en_HK
dc.identifier.issn0270-6474en_HK
dc.identifier.urihttp://hdl.handle.net/10722/132734-
dc.description.abstractThe X-linked form of Charcot-Marie-Tooth disease (CMTX) is associated with mutations in the gene encoding connexin32 (Cx32), which is expressed in Schwann cells. We have compared the functional properties of 11 Cx32 mutations with those of the wild-type protein by testing their ability to form intercellular channels in the paired oocyte expression system. Although seven mutations were functionally incompetent, four others were able to generate intercellular currents of the same order of magnitude as those induced by wild-type Cx32 (Cx32wt). In homotypic oocyte pairs, CMTX mutations retaining functional activity induced the development of junctional currents that exhibited changes in the sensitivity and kinetics of voltage dependence with respect to that of Cx32wt. The four mutations were also capable of interacting in heterotypic configuration with the wild-type protein, and in one case the result was a marked rectification of junctional currents in response to voltage steps of opposite polarity. In addition, the functional CMTX mutations displayed the same selective pattern of compatibility as Cx32wt, interacting with Cx26, Cx46, and Cx50 but failing to do so with Cx40. Although the functional mutations exhibited sensitivity to cytoplasmic acidification, which induced a ≤80% decrease in junctional currents, both the rate and extent of channel closure were enhanced markedly for two of them. Together, these results indicate that the functional consequences of CMTX mutations of Cx32 are of two drastically distinct kinds. The presence of a functional group of mutations suggests that a selective deficit of Cx32 channels may be sufficient to impair the homeostasis of Schwann cells and lead to the development of CMTX.en_HK
dc.languageengen_US
dc.publisherSociety for Neuroscience. The Journal's web site is located at http://www.jneurosci.orgen_HK
dc.relation.ispartofJournal of Neuroscienceen_HK
dc.subjectChannelen_HK
dc.subjectGap junctionen_HK
dc.subjectMyelinen_HK
dc.subjectNeuropathyen_HK
dc.subjectPeripheral nervous systemen_HK
dc.subjectSchwann cellen_HK
dc.titleConnexin32 mutations associated with X-linked Charcot-Marie-Tooth disease show two distinct behaviors: Loss of function and altered gating propertiesen_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.pmid9592087-
dc.identifier.scopuseid_2-s2.0-0032100768en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0032100768&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume18en_HK
dc.identifier.issue11en_HK
dc.identifier.spage4063en_HK
dc.identifier.epage4075en_HK
dc.identifier.isiWOS:000073758400008-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridRessot, C=6603101410en_HK
dc.identifier.scopusauthoridGomès, D=7005538633en_HK
dc.identifier.scopusauthoridDautigny, A=7004049838en_HK
dc.identifier.scopusauthoridPhamDinh, D=7003846115en_HK
dc.identifier.scopusauthoridBruzzone, R=7006793327en_HK

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