scholarly journals Gap junction structure: unraveled, but not fully revealed

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 568 ◽  
Author(s):  
Eric C. Beyer ◽  
Viviana M. Berthoud

Gap junction channels facilitate the intercellular exchange of ions and small molecules, a process that is critical for the function of many different kinds of cells and tissues. Recent crystal structures of channels formed by one connexin isoform (connexin26) have been determined, and they have been subjected to molecular modeling. These studies have provided high-resolution models to gain insights into the mechanisms of channel conductance, molecular permeability, and gating. The models share similarities, but there are some differences in the conclusions reached by these studies. Many unanswered questions remain to allow an atomic-level understanding of intercellular communication mediated by connexin26. Because some domains of the connexin polypeptides are highly conserved (like the transmembrane regions), it is likely that some features of the connexin26 structure will apply to other members of the family of gap junction proteins. However, determination of high-resolution structures and modeling of other connexin channels will be required to account for the diverse biophysical properties and regulation conferred by the differences in their sequences.

2007 ◽  
Vol 3 (3) ◽  
pp. 199-208 ◽  
Author(s):  
Eliana Scemes ◽  
Sylvia O. Suadicani ◽  
Gerhard Dahl ◽  
David C. Spray

AbstractIn this review, we briefly summarize what is known about the properties of the three families of gap junction proteins, connexins, innexins and pannexins, emphasizing their importance as intercellular channels that provide ionic and metabolic coupling and as non-junctional channels that can function as a paracrine signaling pathway. We discuss that two distinct groups of proteins form gap junctions in deuterostomes (connexins) and protostomes (innexins), and that channels formed of the deuterostome homologues of innexins (pannexins) differ from connexin channels in terms of important structural features and activation properties. These differences indicate that the two families of gap junction proteins serve distinct, complementary functions in deuterostomes. In several tissues, including the CNS, both connexins and pannexins are involved in intercellular communication, but have different roles. Connexins mainly contribute by forming the intercellular gap junction channels, which provide for junctional coupling and define the communication compartments in the CNS. We also provide new data supporting the concept that pannexins form the non-junctional channels that play paracrine roles by releasing ATP and, thus, modulating the range of the intercellular Ca2+-wave transmission between astrocytes in culture.


2008 ◽  
Vol 131 (4) ◽  
pp. 293-305 ◽  
Author(s):  
Giedrius Kanaporis ◽  
Gulistan Mese ◽  
Laima Valiuniene ◽  
Thomas W. White ◽  
Peter R. Brink ◽  
...  

Gap junction channels exhibit connexin dependent biophysical properties, including selective intercellular passage of larger solutes, such as second messengers and siRNA. Here, we report the determination of cyclic nucleotide (cAMP) permeability through gap junction channels composed of Cx43, Cx40, or Cx26 using simultaneous measurements of junctional conductance and intercellular transfer of cAMP. For cAMP detection the recipient cells were transfected with a reporter gene, the cyclic nucleotide-modulated channel from sea urchin sperm (SpIH). cAMP was introduced via patch pipette into the cell of the pair that did not express SpIH. SpIH-derived currents (Ih) were recorded from the other cell of a pair that expressed SpIH. cAMP diffusion through gap junction channels to the neighboring SpIH-transfected cell resulted in a five to sixfold increase in Ih current over time. Cyclic AMP transfer was observed for homotypic Cx43 channels over a wide range of conductances. However, homotypic Cx40 and homotypic Cx26 exhibited reduced cAMP permeability in comparison to Cx43. The cAMP/K+ permeability ratios were 0.18, 0.027, and 0.018 for Cx43, Cx26, and Cx40, respectively. Cx43 channels were ∼10 to 7 times more permeable to cAMP than Cx40 or Cx26 (Cx43 > Cx26 ≥ Cx40), suggesting that these channels have distinctly different selectivity for negatively charged larger solutes involved in metabolic/biochemical coupling. These data suggest that Cx43 permeability to cAMP results in a rapid delivery of cAMP from cell to cell in sufficient quantity before degradation by phosphodiesterase to trigger relevant intracellular responses. The data also suggest that the reduced permeability of Cx26 and Cx40 might compromise their ability to deliver cAMP rapidly enough to cause functional changes in a recipient cell.


Author(s):  
Yi-Chia Huang ◽  
Kuan-Han Chen ◽  
Yu-Yang Chen ◽  
Liang-Hsuan Tsao ◽  
Tsung-Han Yeh ◽  
...  

Abstract During oogenesis, a group of specialized follicle cells, known as stretched cells, flatten drastically from cuboidal to squamous shape. While morphogenesis of epithelia is critical for organogenesis, genes and signaling pathways involved in this process remain to be revealed. In addition to formation of gap junctions for intercellular exchange of small molecules, gap junction proteins form channels or act as adaptor proteins to regulate various cellular behaviors. In invertebrates, gap junction proteins are Innexins. Knockdown of Innexin 2 but not other Innexins expressed in follicle cells attenuates stretched cell morphogenesis. Interestingly, blocking of gap junctions with an inhibitor carbenoxolone does not affect stretched cell morphogenesis, suggesting that Innexin 2 might control stretched cell flattening in a gap-junction-independent manner. An excessive level of βPS-Integrin encoded by myospheroid is detected in Innexin 2 mutant cells specifically during stretched cell morphogenesis. Simultaneous knockdown of Innexin 2 and myospheroid partially rescues the morphogenetic defect resulted from Innexin 2 knockdown. Furthermore, reduction of βPS-Integrin is sufficient to induce early stretched cell flattening. Taken together, our data suggest that βPS-Integrin acts downstream of Innexin 2 in modulating stretched cell morphogenesis.


2015 ◽  
Vol 244 (7) ◽  
pp. 903-903 ◽  
Author(s):  
Zeynep F. Altun ◽  
Bojun Chen ◽  
Zhao-Weng Wang ◽  
David H. Hall

Medicina ◽  
2010 ◽  
Vol 46 (1) ◽  
pp. 1 ◽  
Author(s):  
Mindaugas Račkauskas ◽  
Vaidas Neverauskas ◽  
Vytenis Skeberdis

Gap junction channels are composed of two apposing hemichannels (connexons) in the contiguous cells and provide a direct pathway for electrical and metabolic signaling between adjacent cells. The family of connexin genes comprises 20 members in the mouse and 21 genes in the human genome. Connexins are expressed in all tissues except differentiated skeletal muscle, erythrocytes, and mature sperm cells. Various tissues express more than one type of connexins; therefore, homotypic, heterotypic, and heteromeric gap junction channels may form between cells. In this article, we briefly review basic gating and permeability properties of homotypic and heterotypic gap junction channels as well as recent achievements in the research of their regulation by transjunctional voltage, intracellular calcium, pH, and phosphorylation.


2001 ◽  
Vol 280 (5) ◽  
pp. H2103-H2115 ◽  
Author(s):  
Sander Verheule ◽  
Marjan J. A. van Kempen ◽  
Sjoerd Postma ◽  
Martin B. Rook ◽  
Habo J. Jongsma

In comparison to the cellular basis of pacemaking, the electrical interactions mediating synchronization and conduction in the sinoatrial node are poorly understood. Therefore, we have taken a combined immunohistochemical and electrophysiological approach to characterize gap junctions in the nodal area. We report that the pacemaker myocytes in the center of the rabbit sinoatrial node express the gap junction proteins connexin (Cx)40 and Cx46. In the periphery of the node, strands of pacemaker myocytes expressing Cx43 intermingle with strands expressing Cx40 and Cx46. Biophysical properties of gap junctions in isolated pairs of pacemaker myocytes were recorded under dual voltage clamp with the use of the perforated-patch method. Macroscopic junctional conductance ranged between 0.6 and 25 nS with a mean value of 7.5 nS. The junctional conductance did not show a pronounced sensitivity to the transjunctional potential difference. Single-channel recordings from pairs of pacemaker myocytes revealed populations of single-channel conductances at 133, 202, and 241 pS. With these single-channel conductances, the observed average macroscopic junctional conductance, 7.5 nS, would require only 30–60 open gap junction channels.


Author(s):  
William Krakow ◽  
David A. Smith

Recent developments in specimen preparation, imaging and image analysis together permit the experimental determination of the atomic structure of certain, simple grain boundaries in metals such as gold. Single crystal, ∼125Å thick, (110) oriented gold films are vapor deposited onto ∼3000Å of epitaxial silver on (110) oriented cut and polished rock salt substrates. Bicrystal gold films are then made by first removing the silver coated substrate and placing in contact two suitably misoriented pieces of the gold film on a gold grid. Controlled heating in a hot stage first produces twist boundaries which then migrate, so reducing the grain boundary area, to give mixed boundaries and finally tilt boundaries perpendicular to the foil. These specimens are well suited to investigation by high resolution transmission electron microscopy.


Author(s):  
C. J. D. Hetherington

Most high resolution images are not directly interpretable but must be compared with simulations based on model atomic structures and appropriate imaging conditions. Typically, the only parameters that are adjusted, in addition to the structure models, are crystal thickness and microscope defocus. Small tilts of the crystal away from the exact zone axis have only rarely been considered. It is shown here that, in the analysis of an image of a silicon twin intersection, the crystal tilt could be accurately estimated and satisfactorily included in the simulations.The micrograph shown in figure 1 was taken as part of an HREM study of indentation-induced hexagonal silicon. In this instance, the intersection of two twins on different habit planes has driven the silicon into hexagonal stacking. However, in order to confirm this observation, and in order to investigate other defects in the region, it has been necessary to simulate the image taking into account the very apparent crystal tilt. The inability to orientate the specimen at the exact [110] zone was influenced by i) the buckling of the specimen caused by strains at twin intersections, ii) the absence of Kikuchi lines or a clearly visible Laue circle in the diffraction pattern of the thin specimen and iii) the avoidance of radiation damage (which had marked effects on images taken a few minutes later following attempts to realign the crystal.) The direction of the crystal tilt was estimated by observing which of the {111} planes remained close to edge-on to the beam and hence strongly imaged. Further refinement of the direction and magnitude of the tilt was done by comparing simulated images to experimental images in a through-focal series. The presence of three different orientations of the silicon lattice aided the unambiguous determination of the tilt. The final estimate of a 0.8° tilt in the 200Å thick specimen gives atomic columns a projected width of about 3Å.


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