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 Connexin and pannexin mediated cell–cell communication

2007 ◽  
Vol 3 (3) ◽  
pp. 199-208 ◽  
Author(s):  
Eliana Scemes ◽  
Sylvia O. Suadicani ◽  
Gerhard Dahl ◽  
David C. Spray
Keyword(s):  
Gap Junction ◽  
Cell Communication ◽  
Structural Features ◽  
Paracrine Signaling ◽  
Gap Junction Channels ◽  
Metabolic Coupling ◽  
Junctional Coupling ◽  
Intercellular Channels ◽  
Gap Junction Proteins ◽  
Junction Proteins

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.

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.

Ion channnels and transporters in cancer. 5. Ion channels in control of cancer and cell apoptosis

2011 ◽  
Vol 301 (6) ◽  
pp. C1281-C1289 ◽  
Author(s):  
V'yacheslav Lehen'kyi ◽  
George Shapovalov ◽  
Roman Skryma ◽  
Natalia Prevarskaya
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Plasma Membrane ◽  
Ion Channels ◽  
Programmed Cell Death ◽  
Tissue Homeostasis ◽  
Death Rates ◽  
Cellular Processes ◽  
Regulation Of Cell Cycle

Ion channels contribute to virtually all basic cellular processes, including such crucial ones for maintaining tissue homeostasis as proliferation, differentiation, and apoptosis. The involvement of ion channels in regulation of programmed cell death, or apoptosis, has been known for at least three decades based on observation that classical blockers of ion channels can influence cell death rates, prolonging or shortening cell survival. Identification of the central role of these channels in regulation of cell cycle and apoptosis as well as the recent discovery that the expression of ion channels is not limited solely to the plasma membrane, but may also include membranes of internal compartments, has led researchers to appreciate the pivotal role of ion channels plays in development of cancer. This review focuses on the aspects of programmed cell death influenced by various ion channels and how dysfunctions and misregulations of these channels may affect the development and progression of different cancers.

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.

scholarly journals Concatenation of Human Connexin26 (hCx26) and Human Connexin46 (hCx46) for the Analysis of Heteromeric Gap Junction Hemichannels and Heterotypic Gap Junction Channels

2018 ◽  
Vol 19 (9) ◽  
pp. 2742 ◽  
Author(s):  
Patrik Schadzek ◽  
Doris Hermes ◽  
Yannick Stahl ◽  
Nadine Dilger ◽  
Anaclet Ngezahayo
Keyword(s):  
Gap Junction ◽  
Xenopus Oocytes ◽  
Single Channel ◽  
Single Channels ◽  
Dye Transfer ◽  
Channel Conductance ◽  
Gap Junction Channels ◽  
Plaque Area ◽  
Gap Junction Hemichannels ◽  
Inside Out

Gap junction channels and hemichannels formed by concatenated connexins were analyzed. Monomeric (hCx26, hCx46), homodimeric (hCx46-hCx46, hCx26-hCx26), and heterodimeric (hCx26-hCx46, hCx46-hCx26) constructs, coupled to GFP, were expressed in HeLa cells. Confocal microscopy showed that the tandems formed gap junction plaques with a reduced plaque area compared to monomeric hCx26 or hCx46. Dye transfer experiments showed that concatenation allows metabolic transfer. Expressed in Xenopus oocytes, the inside-out patch-clamp configuration showed single channels with a conductance of about 46 pS and 39 pS for hemichannels composed of hCx46 and hCx26 monomers, respectively, when chloride was replaced by gluconate on both membrane sides. The conductance was reduced for hCx46-hCx46 and hCx26-hCx26 homodimers, probably due to the concatenation. Heteromerized hemichannels, depending on the connexin-order, were characterized by substates at 26 pS and 16 pS for hCx46-hCx26 and 31 pS and 20 pS for hCx26-hCx46. Because of the linker between the connexins, the properties of the formed hemichannels and gap junction channels (e.g., single channel conductance) may not represent the properties of hetero-oligomerized channels. However, should the removal of the linker be successful, this method could be used to analyze the electrical and metabolic selectivity of such channels and the physiological consequences for a tissue.

Deubiquitylating enzymes in receptor endocytosis and trafficking

2016 ◽  
Vol 473 (24) ◽  
pp. 4507-4525 ◽  
Author(s):  
Aidan P. McCann ◽  
Christopher J. Scott ◽  
Sandra Van Schaeybroeck ◽  
James F. Burrows
Keyword(s):  
Plasma Membrane ◽  
Ion Channels ◽  
Therapeutic Targets ◽  
Multivesicular Body ◽  
Lysosomal Degradation ◽  
Transmembrane Receptors ◽  
Receptor Endocytosis ◽  
Cellular Processes

In recent times, our knowledge of the roles ubiquitin plays in multiple cellular processes has expanded exponentially, with one example being the role of ubiquitin in receptor endocytosis and trafficking. This has prompted a multitude of studies examining how the different machinery involved in the addition and removal of ubiquitin can influence this process. Multiple deubiquitylating enzymes (DUBs) have been implicated either in facilitating receptor endocytosis and lysosomal degradation or in rescuing receptor levels by preventing endocytosis and/or promoting recycling to the plasma membrane. In this review, we will discuss in detail what is currently known about the role of DUBs in regulating the endocytosis of various transmembrane receptors and ion channels. We will also expand upon the role DUBs play in receptor sorting at the multivesicular body to determine whether a receptor is recycled or trafficked to the lysosome for degradation. Finally, we will briefly discuss how the DUBs implicated in these processes may contribute to the pathogenesis of a range of diseases, and thus the potential these have as therapeutic targets.

scholarly journals Biophysical Properties of Connexin-45 Gap Junction Hemichannels Studied in Vertebrate Cells

2002 ◽  
Vol 119 (2) ◽  
pp. 147-164 ◽  
Author(s):  
Virginijus Valiunas
Keyword(s):  
Gap Junction ◽  
Open Channel ◽  
Lucifer Yellow ◽  
External Solution ◽  
Dye Molecules ◽  
Dye Uptake ◽  
Gap Junction Channels ◽  
Gap Junction Channel ◽  
Cell Recording ◽  
Gap Junction Hemichannels

Human HeLa cells transfected with mouse Cx45 and rat RIN cells transfected with chicken Cx45 were used to study the electrical and permeability properties of Cx45 gap junction hemichannels. With no extracellular Ca2+, whole-cell recording revealed currents arising from hemichannels in both transfected cell lines. Multichannel currents showed a time-dependent activation or deactivation sensitive to voltage, Vm. These currents did not occur in nontransfected cells. The hemichannel currents were inhibited by raising extracellular Ca2+ or by acidification with CO2. The unitary conductance exhibited Vm dependence (i.e., γhc,main increased/decreased with hyperpolarization/depolarization). Extrapolation to Vm = 0 mV led to a γhc,main of 57 pS, roughly twice the conductance of an intact Cx45 gap junction channel. The open channel probability, Po, was Vm-dependent, declining at negative Vm (Po < 0.11, Vm < −50 mV), and increasing at positive Vm (Po ∼0.76, Vm > 50 mV). Moreover, Cx45 nonjunctional hemichannels appeared to mediate lucifer yellow (LY) and propidium iodide (PI) dye uptake from the external solution when extracellular Ca2+ level was reduced. Dye uptake was directly proportional to the number of functioning hemichannels. No significant dye uptake was detected in nontransfected cells. Cx45 transfected HeLa and RIN cells also allowed dye to leak out when preloaded with LY and then incubated in Ca2+-free external solution, whereas little or no dye leakage was observed when these cells were incubated with 2 mM external Ca2+. Intact Cx45 gap junction channels allowed passage of either LY or PI dye, but their respective flux rates were different. Comparison of LY diffusion through Cx45 hemichannels and intact gap junction channels revealed that the former is more permeable, suggesting that gap junction channel pores exhibit more allosterical restriction to the dye molecules than the unopposed hemichannel. The data demonstrate the opening of Cx45 nonjunctional hemichannels in vertebrate cells when the external Ca2+ concentration is reduced.

vitreal cells and specialized phagocytes in the chick embryo retina: A TEM and SEM study

1990 ◽  
Vol 48 (3) ◽  
pp. 330-331
Author(s):  
M.A. Cuadros ◽  
M.J. Martinez-Guerrero ◽  
A. Rios
Keyword(s):  
Cell Death ◽  
Plasma Membrane ◽  
Acid Phosphatase ◽  
Chick Embryo ◽  
Basement Membrane ◽  
Sem Images ◽  
Intimate Contact ◽  
Cellular Processes ◽  
Sem Study ◽  
Free Cells

In the chick embryo retina (days 3-4 of incubation), coinciding with an increase in cell death, specialized phagocytes characterized by intense acid phosphatase activity have been described. In these preparations, all free cells in the vitreal humor (vitreal cells) were strongly labeled. Conventional TEM and SEM techniques were used to characterize them and attempt to determine their relationship with retinal phagocytes.Two types of vitreal cells were distinguished. The first are located at some distance from the basement membrane of the neuroepithelium, and are rounded, with numerous vacuoles and thin cytoplasmic prolongations. Images of exo- and or endocytosis were frequent; the cells showed a well-developed Golgi apparatus (Fig. 1) In SEM images, the cells was covered with short cellular processes (Fig. 3). Cells lying parallel to or alongside the basement membrane are elongated. The plasma membrane is frequently in intimate contact with the basement membrane. These cells have generally a large cytoplasmic expansion (Fig. 5).

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