Human Molecular Genetics Advance Access published online on October 28, 2003
Human Molecular Genetics, doi:10.1093/hmg/ddg364
© 2003 by Oxford University Press
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Laboratory of Cutaneous Biology, Dermatogenetic, CHUV, 1011 Lausanne, Switzerland
* To whom correspondence should be addressed. E-mail: daniel.hohl{at}hospvd.ch.
Connexins are homologous four-transmembrane-domain proteins and major components of gap junctions. We recently identified mutations in either GJB3 or GJB4 genes, encoding respectively connexin 31 (Cx31) or 30.3 (Cx30.3), to be causally involved in erythrokeratodermia variabilis (EKV), a mostly autosomal dominant disorder of keratinization. Despite slight differences, phenotypes of EKV Mendes Da Costa (Cx31) and EKV Cram-Mevorah (Cx30.3) show major clinical overlap and both Cx30.3 and Cx31 are expressed in the upper epidermal layers. These similarities suggested to us that Cx30.3 and Cx31 may interact at a molecular level. Indeed, expression of wild type Cx30.3 in HeLa cell resulted only in minor amounts of protein addressed to the plasma membrane. Mutant Cx30.3 was hardly detectable and disturbed intercellular coupling. In sharp contrast, co-expression of both wild type proteins led to a gigantic increase of stabilized heteromeric gap junctions. Furthermore, co-expressed wild type Cx30.3 and Cx31 coprecipitate which demonstrates a physical interaction. Inhibitor experiments revealed that this interaction begins in the endoplasmic reticulum. These results not only provide new insights into epidermal connexin synthesis and polymerization but also allow a novel molecular explanation for the similarity of EKV phenotypes.
Article
Molecular interaction of connexin 30.3 and connexin 31 suggests a dominant-negative mechanism associated with EKV
2 Dept of Morphology, CMU, 1211 Geneva, Switzerland
3 Laboratory for Cutaneous Biology, Dermatogenetic Unit, CHUV-BT 437, CH-1011 Lausanne, Switzerland
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  I. Sargiannidou, N. Vavlitou, S. Aristodemou, A. Hadjisavvas, K. Kyriacou, S. S. Scherer, and K. A. Kleopa Connexin32 Mutations Cause Loss of Function in Schwann Cells and Oligodendrocytes Leading to PNS and CNS Myelination Defects J. Neurosci., April 15, 2009; 29(15): 4736 - 4749. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Schnichels, P. Worsdorfer, R. Dobrowolski, C. Markopoulos, M. Kretz, G. Schwarz, E. Winterhager, and K. Willecke The Connexin31 F137L mutant mouse as a model for the human skin disease Erythrokeratodermia variabilis (EKV) Hum. Mol. Genet., May 15, 2007; 16(10): 1216 - 1224. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. L. Shurman, L. Glazewski, A. Gumpert, J. D. Zieske, and G. Richard In Vivo and In Vitro Expression of Connexins in the Human Corneal Epithelium Invest. Ophthalmol. Vis. Sci., June 1, 2005; 46(6): 1957 - 1965. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.-L. Di, Y. Gu, J. E. A. Common, T. Aasen, E. A. O'Toole, D. P. Kelsell, and D. Zicha Connexin interaction patterns in keratinocytes revealed morphologically and by FRET analysis J. Cell Sci., April 1, 2005; 118(7): 1505 - 1514. [Abstract] [Full Text] [PDF]
|
|