What is hidden in the pannexin treasure trove: the sneak peek and the guesswork

Litvin, Oxana

doi:10.2755/jcmm010.003.04

Cited by 9 publications

(14 citation statements)

References 91 publications

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“…ATP release was measured 5, 10, and 15 min after addition of Ilo (1 M) to erythrocytes that were preincubated with carbenoxolone (100 M, n ϭ 6; A), probenecid (100 M, n ϭ 6; B), 10 Other candidates for ATP conduits include other ATPbinding cassette proteins (MDR1) (2), maxi anion channels (27), connexins (10,11), and, more recently, pannexins (4,22,36). Pannexin 1 is classified as a "gap junction protein" because of the sequence homology it shares with innexins (23,26). Pannexins form channels with properties that make them attractive candidates for ATP conduits.…”

Section: Discussionmentioning

confidence: 99%

Pannexin 1 is the conduit for low oxygen tension-induced ATP release from human erythrocytes

Sridharan

Adderley

Bowles

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

164

179

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is the conduit for low oxygen tension-induced ATP release from human erythrocytes. Am J Physiol Heart Circ Physiol 299: H1146 -H1152, 2010. First published July 9, 2010; doi:10.1152/ajpheart.00301.2010.-Erythrocytes release ATP in response to exposure to the physiological stimulus of lowered oxygen (O 2) tension as well as pharmacological activation of the prostacyclin receptor (IPR). ATP release in response to these stimuli requires activation of adenylyl cyclase, accumulation of cAMP, and activation of protein kinase A. The mechanism by which ATP, a highly charged anion, exits the erythrocyte in response to lowered O 2 tension or receptor-mediated IPR activation by iloprost is unknown. It was demonstrated previously that inhibiting pannexin 1 with carbenoxolone inhibits hypotonically induced ATP release from human erythrocytes. Here we demonstrate that three structurally dissimilar compounds known to inhibit pannexin 1 prevent ATP release in response to lowered O 2 tension but not to iloprost-induced ATP release. These results suggest that pannexin 1 is the conduit for ATP release from erythrocytes in response to lowered O 2 tension. However, the identity of the conduit for iloprost-induced ATP release remains unknown.iloprost; carbenoxolone; probenecid; red blood cell; cystic fibrosis transmembrane conductance regulator ERYTHROCYTES CONTRIBUTE to the regulation of vascular caliber by virtue of their ability to release adenosine 5=-triphosphate (ATP) (14 -17, 48, 50). ATP released from erythrocytes binds to purinergic receptors on the vascular endothelium, which leads to the local formation of endothelium-derived vasodilators such as nitric oxide, prostaglandins, and endotheliumderived hyperpolarizing factor (20,46,50).Erythrocytes release ATP in response to mechanical deformation and exposure to lowered oxygen (O 2 ) tension and in response to incubation with pharmacological agents such as the prostacyclin analog iloprost (Ilo) (5,44,45). ATP release in response to these various stimuli requires activation of adenylyl cyclase, accumulation of cAMP, and activation of PKA (3,43,47). Although several components of the signaling pathway for ATP release from erythrocytes have been investigated, the identity of the conduit by which ATP exits these cells is not fully characterized. In other cell types, several membrane channels, including connexin hemichannels, voltage-dependent anion channels, volume-regulated anion channels, and ATP-binding cassette proteins, have been implicated as conduits for ATP release (2,27,29,37,40,41). In addition, the cystic fibrosis transmembrane conductance regulator (CFTR), an ATP-binding cassette protein required for ATP release from erythrocytes in response to mechanical deformation (25, 45), was once considered to be a possible ATP conduit in cells. However, more recent studies demonstrate that CFTR is not likely to serve as an ATP conduit itself but rather regulates other channels that serve that role (1,7,19,24,51).Recently, the protein family of pannexins, orthologs of the invert...

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Section: Discussionmentioning

confidence: 99%

Pannexin 1 is the conduit for low oxygen tension-induced ATP release from human erythrocytes

Sridharan

Adderley

Bowles

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

164

179

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“…21 Moreover, such an interaction may not be physiologically relevant, as these Panxs have not yet been identified to endogenously co-exist within the same cell type. 5,[45][46][47] Thus, while Panx intermixing represents a putative regulatory mechanism for anterograde Panx trafficking, further information regarding endogenous co-expression profiles of Panx family members is required to fully appreciate its significance.…”

Section: Does Panx Subunit Intermixing Occur Endogenously?mentioning

confidence: 99%

Pore positioning

et al. 2013

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“…Pannexin1 (panx1) forms junctional channels when overexpressed in the Xenopus oocyte system and in at least one cell line (vanden Abeele et al, 2006). Pannexin gene and/or protein expression have been demonstrated in a wide variety of tissues Baranova et al, 2004;Dvoriantchikova et al, 2006;Litvin et al, 2006;Locovei et al, 2006,Ray et al, 2006, but expression of panx1 in most cell types used in permeability studies to date has not been directly assessed. This raises the possibility that junctional permeability mediated by pannexin channels could contribute to permeability that has been attributed to connexin channels, particularly if expression of the two proteins is positively correlated.…”

Section: Junctional Channelsmentioning

confidence: 99%

Connexin channel permeability to cytoplasmic molecules

Harris¹

2007

Progress in Biophysics and Molecular Biology

410

346

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Connexin channels are known to be permeable to a variety of cytoplasmic molecules. The first observation of second messenger junctional permeability, made ∼30 years ago, sparked broad interest in gap junction channels as mediators of intercellular molecular signaling. Since then, much has been learned about the diversity of connexin channels with regard to isoform diversity, tissue and developmental distribution, modes of channel regulation, assembly and expression, biochemical modification and permeability, all of which appear to be dynamically regulated. This information has expanded the potential roles of connexin channels in development, physiology and disease, and made their elucidation much more complex -30 years ago such an orchestra of junctional dynamics was unanticipated. Only recently, however, have investigators been able to directly address, in this more complex framework, the key issue: What specific biological molecules, second messengers and others, are able to permeate the various types of connexin channels, and how well? An important related issue, given the ever-growing list of connexin-related pathologies, is how these permeabilities are altered by disease-causing connexin mutations. Together, many studies show that a variety of cytoplasmic molecules can permeate the different types of connexin channels. A few studies reveal differences in permeation by different molecules through a particular type of connexin channel, and differences in permeation by a particular molecule through different types of connexin channels. This article describes and evaluates the various methods used to obtain these data, presents an annotated compilation of the results, and discusses the findings in the context of what can be inferred about mechanism of selectivity and potential relevance to signaling. The data strongly suggest that highly specific interactions take place between connexin pores and specific biological molecular permeants, and that those interactions determine which cytoplasmic molecules can permeate and how well. At this time, the nature of those interactions is unclear. One hopes that with more detailed permeability and structural information, the specific molecular mechanisms of the selectivity can be elucidated.

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What is hidden in the pannexin treasure trove: the sneak peek and the guesswork

Cited by 9 publications

References 91 publications

Pannexin 1 is the conduit for low oxygen tension-induced ATP release from human erythrocytes

Pannexin 1 is the conduit for low oxygen tension-induced ATP release from human erythrocytes

Pore positioning

Connexin channel permeability to cytoplasmic molecules

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