Selective defects in channel permeability associated with Cx32 mutations causing X-linked Charcot–Marie–Tooth disease
The X-linked form of Charcot–Marie–Tooth disease (CMTX) is caused by mutations in connexin32 (Cx32), a gap junction protein expressed by Schwann cells where it forms reflexive channels that allow the passage of ions and signaling molecules across the myelin sheath. Although most mutations result in...
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2006-03-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996105002482 |
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doaj-741a3734d44e4270b3b0d4deec9b8d262021-03-20T04:52:02ZengElsevierNeurobiology of Disease1095-953X2006-03-01213607617Selective defects in channel permeability associated with Cx32 mutations causing X-linked Charcot–Marie–Tooth diseaseMassimiliano Bicego0Sabina Morassutto1Victor H. Hernandez2Marcello Morgutti3Fabio Mammano4Paola D'Andrea5Roberto Bruzzone6Dipartimento di Biochimica, Biofisica e Chimica delle Macromolecole, University of Trieste, via Licio Giorgieri 1, 34127 Trieste, ItalyDipartimento di Biochimica, Biofisica e Chimica delle Macromolecole, University of Trieste, via Licio Giorgieri 1, 34127 Trieste, ItalyVenetian Institute of Molecular Medicine, 35129 Padua, ItalyServizio di Genetica, IRCCS “Burlo Garofolo” di Trieste, 34100 Trieste, ItalyVenetian Institute of Molecular Medicine, 35129 Padua, ItalyDipartimento di Biochimica, Biofisica e Chimica delle Macromolecole, University of Trieste, via Licio Giorgieri 1, 34127 Trieste, Italy; Corresponding authors. Paola D'Andrea is to be contacted at Dipartimento di Biochimica, Biofisica e Chimica delle Macromolecole, University of Trieste, via Licio Giorgieri 1, 34127 Trieste, Italy. Fax: +39 040 676 3691. Roberto Bruzzone, Department of Neuroscience, Institut Pasteur, 25, rue du Dr. Roux, 75015 Paris, France. Fax: +33 1 4061 3421.Department of Neuroscience, Institut Pasteur, 25, rue du Dr. Roux, 75015 Paris, France; Corresponding authors. Paola D'Andrea is to be contacted at Dipartimento di Biochimica, Biofisica e Chimica delle Macromolecole, University of Trieste, via Licio Giorgieri 1, 34127 Trieste, Italy. Fax: +39 040 676 3691. Roberto Bruzzone, Department of Neuroscience, Institut Pasteur, 25, rue du Dr. Roux, 75015 Paris, France. Fax: +33 1 4061 3421.The X-linked form of Charcot–Marie–Tooth disease (CMTX) is caused by mutations in connexin32 (Cx32), a gap junction protein expressed by Schwann cells where it forms reflexive channels that allow the passage of ions and signaling molecules across the myelin sheath. Although most mutations result in loss of function, several studies have reported that some retain the ability to form homotypic intercellular channels. To gain insight into the molecular defect of three functional CMTX variants, S26L, Δ111–116 and R220stop, we have used several fluorescent tracers of different size and ionic charge to compare their permeation properties to those of wild-type Cx32. Although all mutations allowed the passage of the dye with the smallest molecular mass, they exhibited a clear reduction in the permeability of either one or all of the probes with respect to wild-type channels, as assessed by the percentage of injections showing dye coupling. These data reveal that a lower size cutoff distinguishes these functional CMTX variants from wild-type channels and suggest that this defect may be of pathophysiological relevance.http://www.sciencedirect.com/science/article/pii/S0969996105002482ConnexinDye couplingGap junctionGenetic diseaseHumanPNS |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Massimiliano Bicego Sabina Morassutto Victor H. Hernandez Marcello Morgutti Fabio Mammano Paola D'Andrea Roberto Bruzzone |
| spellingShingle |
Massimiliano Bicego Sabina Morassutto Victor H. Hernandez Marcello Morgutti Fabio Mammano Paola D'Andrea Roberto Bruzzone Selective defects in channel permeability associated with Cx32 mutations causing X-linked Charcot–Marie–Tooth disease Neurobiology of Disease Connexin Dye coupling Gap junction Genetic disease Human PNS |
| author_facet |
Massimiliano Bicego Sabina Morassutto Victor H. Hernandez Marcello Morgutti Fabio Mammano Paola D'Andrea Roberto Bruzzone |
| author_sort |
Massimiliano Bicego |
| title |
Selective defects in channel permeability associated with Cx32 mutations causing X-linked Charcot–Marie–Tooth disease |
| title_short |
Selective defects in channel permeability associated with Cx32 mutations causing X-linked Charcot–Marie–Tooth disease |
| title_full |
Selective defects in channel permeability associated with Cx32 mutations causing X-linked Charcot–Marie–Tooth disease |
| title_fullStr |
Selective defects in channel permeability associated with Cx32 mutations causing X-linked Charcot–Marie–Tooth disease |
| title_full_unstemmed |
Selective defects in channel permeability associated with Cx32 mutations causing X-linked Charcot–Marie–Tooth disease |
| title_sort |
selective defects in channel permeability associated with cx32 mutations causing x-linked charcot–marie–tooth disease |
| publisher |
Elsevier |
| series |
Neurobiology of Disease |
| issn |
1095-953X |
| publishDate |
2006-03-01 |
| description |
The X-linked form of Charcot–Marie–Tooth disease (CMTX) is caused by mutations in connexin32 (Cx32), a gap junction protein expressed by Schwann cells where it forms reflexive channels that allow the passage of ions and signaling molecules across the myelin sheath. Although most mutations result in loss of function, several studies have reported that some retain the ability to form homotypic intercellular channels. To gain insight into the molecular defect of three functional CMTX variants, S26L, Δ111–116 and R220stop, we have used several fluorescent tracers of different size and ionic charge to compare their permeation properties to those of wild-type Cx32. Although all mutations allowed the passage of the dye with the smallest molecular mass, they exhibited a clear reduction in the permeability of either one or all of the probes with respect to wild-type channels, as assessed by the percentage of injections showing dye coupling. These data reveal that a lower size cutoff distinguishes these functional CMTX variants from wild-type channels and suggest that this defect may be of pathophysiological relevance. |
| topic |
Connexin Dye coupling Gap junction Genetic disease Human PNS |
| url |
http://www.sciencedirect.com/science/article/pii/S0969996105002482 |
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