Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Cell Sci
2008 Aug 15;121Pt 16:2744-50. doi: 10.1242/jcs.032482.
Show Gene links
Show Anatomy links
An intact connexin N-terminus is required for function but not gap junction formation.
Kyle JW
,
Minogue PJ
,
Thomas BC
,
Domowicz DA
,
Berthoud VM
,
Hanck DA
,
Beyer EC
.
???displayArticle.abstract???
The cytoplasmic N-termini of connexins have been implicated in protein trafficking, oligomerization and channel gating. To elucidate the role of the N-terminus in connexin37 (CX37), we studied mutant constructs containing partial deletions of its 23 N-terminal amino acids and a construct with a complete N-terminus in which residues 2-8 were replaced with alanines. All mutants containing nine or more N-terminal amino acids form gap junction plaques in transiently transfected HeLa cells, whereas most of the longer deletions do not. Although wild-type CX37 allowed intercellular transfer of microinjected neurobiotin in HeLa cells and formed conducting hemichannels in Xenopus oocytes, none of the mutant constructs tested show evidence of channel function. However, in coexpression experiments, N-terminal mutants that formed gap junction plaques potently inhibit hemichannel conductance of wild-type CX37 suggesting their co-oligomerization. We conclude that as much as half the length of the connexin N-terminus can be deleted without affecting formation of gap junction plaques, but an intact N-terminus is required for hemichannel gating and intercellular communication.
Barrio,
Gap junctions formed by connexins 26 and 32 alone and in combination are differently affected by applied voltage.
1991, Pubmed,
Xenbase
Barrio,
Gap junctions formed by connexins 26 and 32 alone and in combination are differently affected by applied voltage.
1991,
Pubmed
,
Xenbase
Chang,
A Gja8 (Cx50) point mutation causes an alteration of alpha 3 connexin (Cx46) in semi-dominant cataracts of Lop10 mice.
2002,
Pubmed
Common,
Cellular mechanisms of mutant connexins in skin disease and hearing loss.
2003,
Pubmed
D'Andrea,
Hearing loss: frequency and functional studies of the most common connexin26 alleles.
2002,
Pubmed
Deschênes,
Altered trafficking of mutant connexin32.
1997,
Pubmed
Dong,
Role of the N-terminus in permeability of chicken connexin45.6 gap junctional channels.
2006,
Pubmed
Ebihara,
Distinct behavior of connexin56 and connexin46 gap junctional channels can be predicted from the behavior of their hemi-gap-junctional channels.
1995,
Pubmed
,
Xenbase
Essenfelder,
Connexin30 mutations responsible for hidrotic ectodermal dysplasia cause abnormal hemichannel activity.
2004,
Pubmed
,
Xenbase
Grifa,
Mutations in GJB6 cause nonsyndromic autosomal dominant deafness at DFNA3 locus.
1999,
Pubmed
,
Xenbase
Lagree,
Specific amino-acid residues in the N-terminus and TM3 implicated in channel function and oligomerization compatibility of connexin43.
2003,
Pubmed
Larson,
Functional expression and biochemical characterization of an epitope-tagged connexin37.
2000,
Pubmed
Larson,
Differential regulation of connexin43 and connexin37 in endothelial cells by cell density, growth, and TGF-beta1.
1997,
Pubmed
Matsuyama,
Phenotypes of X-linked Charcot-Marie-Tooth disease and altered trafficking of mutant connexin 32 (GJB1).
2001,
Pubmed
Musa,
Amino terminal glutamate residues confer spermine sensitivity and affect voltage gating and channel conductance of rat connexin40 gap junctions.
2004,
Pubmed
Oh,
Stoichiometry of transjunctional voltage-gating polarity reversal by a negative charge substitution in the amino terminus of a connexin32 chimera.
2000,
Pubmed
,
Xenbase
Oshima,
Roles of Met-34, Cys-64, and Arg-75 in the assembly of human connexin 26. Implication for key amino acid residues for channel formation and function.
2003,
Pubmed
Oshima,
Three-dimensional structure of a human connexin26 gap junction channel reveals a plug in the vestibule.
2007,
Pubmed
Pal,
Molecular mechanism underlying a Cx50-linked congenital cataract.
1999,
Pubmed
,
Xenbase
Paznekas,
Connexin 43 (GJA1) mutations cause the pleiotropic phenotype of oculodentodigital dysplasia.
2003,
Pubmed
Puljung,
Polyvalent cations constitute the voltage gating particle in human connexin37 hemichannels.
2004,
Pubmed
,
Xenbase
Purnick,
Structure of the amino terminus of a gap junction protein.
2000,
Pubmed
,
Xenbase
Purnick,
Reversal of the gating polarity of gap junctions by negative charge substitutions in the N-terminus of connexin 32.
2000,
Pubmed
,
Xenbase
Reed,
Molecular cloning and functional expression of human connexin37, an endothelial cell gap junction protein.
1993,
Pubmed
Ressot,
Connexin32 mutations associated with X-linked Charcot-Marie-Tooth disease show two distinct behaviors: loss of function and altered gating properties.
1998,
Pubmed
,
Xenbase
Richard,
Genetic heterogeneity in erythrokeratodermia variabilis: novel mutations in the connexin gene GJB4 (Cx30.3) and genotype-phenotype correlations.
2003,
Pubmed
Rouan,
Divergent effects of two sequence variants of GJB3 (G12D and R32W) on the function of connexin 31 in vitro.
2003,
Pubmed
Satin,
The cloned cardiac Na channel alpha-subunit expressed in Xenopus oocytes show gating and blocking properties of native channels.
1992,
Pubmed
,
Xenbase
Shibayama,
Functional characterization of connexin43 mutations found in patients with oculodentodigital dysplasia.
2005,
Pubmed
Srinivas,
Correlative studies of gating in Cx46 and Cx50 hemichannels and gap junction channels.
2005,
Pubmed
,
Xenbase
Thomas,
Cataracts are caused by alterations of a critical N-terminal positive charge in connexin50.
2008,
Pubmed
Tong,
Exchange of gating properties between rat cx46 and chicken cx45.6.
2004,
Pubmed
,
Xenbase
Tong,
Structural determinants for the differences in voltage gating of chicken Cx56 and Cx45.6 gap-junctional hemichannels.
2006,
Pubmed
,
Xenbase
Trexler,
Voltage gating and permeation in a gap junction hemichannel.
1996,
Pubmed
,
Xenbase
Unger,
Three-dimensional structure of a recombinant gap junction membrane channel.
1999,
Pubmed
Veenstra,
Connexin37 forms high conductance gap junction channels with subconductance state activity and selective dye and ionic permeabilities.
1994,
Pubmed
Verselis,
Opposite voltage gating polarities of two closely related connexins.
1994,
Pubmed
,
Xenbase
Willoughby,
A novel GJA8 mutation in an Iranian family with progressive autosomal dominant congenital nuclear cataract.
2003,
Pubmed
Wong,
Connexin37 protects against atherosclerosis by regulating monocyte adhesion.
2006,
Pubmed
