Plasma Membrane Channels Formed by Connexins: Their Regulation and Functions

2003 ◽  
Vol 83 (4) ◽  
pp. 1359-1400 ◽  
Author(s):  
JUAN C. SÁEZ ◽  
VIVIANA M. BERTHOUD ◽  
MARÍA C. BRAÑES ◽  
AGUSTÍN D. MARTÍNEZ ◽  
ERIC C. BEYER
Keyword(s):  
Plasma Membrane ◽  
Gap Junction ◽  
Protein Trafficking ◽  
Genetic Diseases ◽  
Physiological Role ◽  
Channel Structure ◽  
Membrane Channels ◽  
Intercellular Signaling ◽  
Gap Junction Channels ◽  
Extracellular Milieu

Sáez, Juan C., Viviana M. Berthoud, María C. Brañes, Agustín D. Martínez, and Eric C. Beyer. Plasma Membrane Channels Formed by Connexins: Their Regulation and Functions. Physiol Rev 83: 1359-1400, 2003; 10.1152/physrev.00007.2003.—Members of the connexin gene family are integral membrane proteins that form hexamers called connexons. Most cells express two or more connexins. Open connexons found at the nonjunctional plasma membrane connect the cell interior with the extracellular milieu. They have been implicated in physiological functions including paracrine intercellular signaling and in induction of cell death under pathological conditions. Gap junction channels are formed by docking of two connexons and are found at cell-cell appositions. Gap junction channels are responsible for direct intercellular transfer of ions and small molecules including propagation of inositol trisphosphate-dependent calcium waves. They are involved in coordinating the electrical and metabolic responses of heterogeneous cells. New approaches have expanded our knowledge of channel structure and connexin biochemistry (e.g., protein trafficking/assembly, phosphorylation, and interactions with other connexins or other proteins). The physiological role of gap junctions in several tissues has been elucidated by the discovery of mutant connexins associated with genetic diseases and by the generation of mice with targeted ablation of specific connexin genes. The observed phenotypes range from specific tissue dysfunction to embryonic lethality.

Mechanical stimulation initiates cell-to-cell calcium signaling in ovine lens epithelial cells

1996 ◽  
Vol 109 (2) ◽  
pp. 355-365 ◽  
Author(s):  
G.C. Churchill ◽  
M.M. Atkinson ◽  
C.F. Louis
Keyword(s):  
Plasma Membrane ◽  
Epithelial Cells ◽  
Gap Junction ◽  
Mechanical Stimulation ◽  
Primary Cultures ◽  
Channel Blockers ◽  
Extracellular Medium ◽  
Gap Junction Channels ◽  
Cell Propagation ◽  
Cytosolic Factor

Although abnormalities in calcium regulation have been implicated in the development of most forms of cataract, the mechanisms by which Ca2+ is regulated in the cells of the ocular lens remain poorly defined. Cell-to-cell Ca2+ signaling was investigated in primary cultures of ovine epithelial cells using the Ca(2+)-reporter dye fura-2 and fluorescence microscopy. Mechanical stimulation of a single cell with a micropipette initiated a propagated increase in cytosolic free Ca2+ that spread from the stimulated cell through 2–8 tiers of surrounding cells. During this intercellular Ca2+ wave, cytosolic Ca2+ increased 2- to 12-fold from resting levels of approximately 100 nM. Nanomolar extracellular Ca2+ did not affect the cell-to-cell propagation of the Ca2+ wave, but reduced the magnitude of the cytosolic Ca2+ increases, which was most evident in the mechanically-stimulated cell. Depletion of intracellular Ca2+ stores with thapsigargin eliminated the propagated intercellular Ca2+ wave, but did not prevent the cytosolic Ca2+ increase in the mechanically-stimulated cell, which required extracellular Ca2+ and was attenuated by the addition of the Ca2+ channel blockers Ni2+, Gd3+ and La3+ to the medium. These results are most easily explained by a mechanically-activated channel in the plasma membrane of the stimulated cell. The propagated increase in cytosolic Ca2+ appeared to be communicated to adjacent cells by the passage of an intracellular messenger other than Ca2+ through gap junction channels. However, if the plasma membrane of the mechanically-stimulated cell was ruptured such that there was loss of cytosolic contents, the increase in cytosolic Ca2+ in the surrounding cells was elicited by both a messenger passing through gap junction channels and by a cytosolic factor(s) diffusing through the extracellular medium. These results demonstrate the existence of intercellular Ca2+ signaling in lens cells, which may play a role in regulating cytosolic Ca2+ in the intact lens.

New Roles for Connexons

Physiology ◽  
2003 ◽  
Vol 18 (3) ◽  
pp. 100-103 ◽  
Author(s):  
Lisa Ebihara
Keyword(s):  
Plasma Membrane ◽  
Ion Channels ◽  
Gap Junction ◽  
Paracrine Signaling ◽  
Gap Junction Channels ◽  
Cellular Processes ◽  
Gap Junction Hemichannels

Connexons or gap junction hemichannels are large, nonselective ion channels that reside in the nonjunctional plasma membrane before their assembly into gap junction channels. Increasing evidence suggests that these channels can open under certain conditions and may participate in a number of cellular processes, including the release of small metabolites such as ATP and NAD+, which are involved in paracrine signaling.

scholarly journals Identification and classification of innexin gene transcripts in the central nervous system of the terrestrial slug Limax valentianus

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0244902
Author(s):  
Hisayo Sadamoto ◽  
Hironobu Takahashi ◽  
Suguru Kobayashi ◽  
Hirooki Kondoh ◽  
Hiroshi Tokumaru
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Gap Junction ◽  
Circular Rna ◽  
Electrical Synapse ◽  
Sequence Information ◽  
Membrane Channels ◽  
Gap Junction Channels ◽  
The Central Nervous System

Intercellular gap junction channels and single-membrane channels have been reported to regulate electrical synapse and the brain function. Innexin is known as a gap junction-related protein in invertebrates and is involved in the formation of intercellular gap junction channels and single-cell membrane channels. Multiple isoforms of innexin protein in each species enable the precise regulation of channel function. In molluscan species, sequence information of innexins is still limited and the sequences of multiple innexin isoforms have not been classified. This study examined the innexin transcripts expressed in the central nervous system of the terrestrial slug Limax valentianus and identified 16 transcripts of 12 innexin isoforms, including the splicing variants. We performed phylogenetic analysis and classified the isoforms with other molluscan innexin sequences. Next, the phosphorylation, N-glycosylation, and S-nitrosylation sites were predicted to characterize the innexin isoforms. Further, we identified 16 circular RNA sequences of nine innexin isoforms in the central nervous system of Limax. The identification and classification of molluscan innexin isoforms provided novel insights for understanding the regulatory mechanism of innexin in this phylum.

scholarly journals Regulation of Hemichannels and Gap Junction Channels by Cytokines in Antigen-Presenting Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-23 ◽  
Author(s):  
Pablo J. Sáez ◽  
Kenji F. Shoji ◽  
Adam Aguirre ◽  
Juan C. Sáez
Keyword(s):  
Immune System ◽  
Gap Junction ◽  
Immune Cells ◽  
Intercellular Communication ◽  
Purinergic Signaling ◽  
Antigen Presenting Cells ◽  
Cell Types ◽  
Gap Junction Channels ◽  
Extracellular Milieu ◽  
Antigen Presenting

Autocrine and paracrine signals coordinate responses of several cell types of the immune system that provide efficient protection against different challenges. Antigen-presenting cells (APCs) coordinate activation of this system via homocellular and heterocellular interactions. Cytokines constitute chemical intercellular signals among immune cells and might promote pro- or anti-inflammatory effects. During the last two decades, two membrane pathways for intercellular communication have been demonstrated in cells of the immune system. They are called hemichannels (HCs) and gap junction channels (GJCs) and provide new insights into the mechanisms of the orchestrated response of immune cells. GJCs and HCs are permeable to ions and small molecules, including signaling molecules. The direct intercellular transfer between contacting cells can be mediated by GJCs, whereas the release to or uptake from the extracellular milieu can be mediated by HCs. GJCs and HCs can be constituted by two protein families: connexins (Cxs) or pannexins (Panxs), which are present in almost all APCs, being Cx43 and Panx1 the most ubiquitous members of each protein family. In this review, we focus on the effects of different cytokines on the intercellular communication mediated by HCs and GJCs in APCs and their impact on purinergic signaling.

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