Pannexin channels are not gap junction hemichannels

Sosinsky, Gina E.; Boassa, Daniela; Dermietzel, Rolf; Duffy, Heather S.; Laird, Dale W.; MacVicar, Brian A.; Naus, Christian C.; Peñuela, Silvia; Scemes, Eliana; Spray, David C.; Thompson, Roger; Zhao, Hong Bo; Dahl, Gerhard

doi:10.4161/chan.5.3.15765

Cited by 319 publications

(276 citation statements)

References 36 publications

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“…However, innexins and connexins have no evolutionary relationship (59,61,62,65,66). In contrast, pannexins are vertebrate homologs of innexins (59,67,68), but they do not form gap junctions, functioning instead as unapposed plasma membrane ion channels (69). Connexons (29,36) and pannexins (Panx1 (70)) are hexameric assemblies of subunits.…”

Section: Similarities Of Calhm1 Connexins and Pannexins/innexinsmentioning

confidence: 99%

Structural and Functional Similarities of Calcium Homeostasis Modulator 1 (CALHM1) Ion Channel with Connexins, Pannexins, and Innexins*

Siebert¹,

Ma²,

Grevet³

et al. 2013

Journal of Biological Chemistry

109

122

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Background: CALHM1 is an ion channel for which structural information is lacking. Results: CALHM1 has poor ion selectivity and a wide (ϳ14 Å) pore and is a hexamer, with monomers having four transmembrane domains with cytoplasmic termini. Conclusion: CALHM1 shares structural features with pannexins, connexins, and innexins. Significance: CALHMs, connexins, and pannexins/innexins are three structurally related protein families with shared and distinct functional properties.

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Section: Similarities Of Calhm1 Connexins and Pannexins/innexinsmentioning

confidence: 99%

Structural and Functional Similarities of Calcium Homeostasis Modulator 1 (CALHM1) Ion Channel with Connexins, Pannexins, and Innexins*

Siebert¹,

Ma²,

Grevet³

et al. 2013

Journal of Biological Chemistry

109

122

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“…Initial expectations that pannexins might also incorporate into intercellular gap junctions have given way to current views that they instead form membrane channels (3). Among the three members of the pannexin family, pannexin 1 (PANX1) 2 has garnered the most attention.…”

mentioning

confidence: 99%

Pannexin 1, an ATP Release Channel, Is Activated by Caspase Cleavage of Its Pore-associated C-terminal Autoinhibitory Region

Sandilos

Chiu

Chekeni

et al. 2012

Journal of Biological Chemistry

267

311

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Background: Pannexin 1 is activated by caspase cleavage of its C-terminal tail during apoptosis. Results: Cleavage removes a critical adjacent region to activate membrane-associated PANX1; activation requires dissociation of the C terminus from the pore. Conclusion: An intrinsic inhibitory interaction between the C terminus and the pore constrains PANX1 activity. Significance: PANX1 activation is caused by disruption of C-terminal-mediated inhibition.

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“…1 Although originally thought to constitute a brand new family of gap junction proteins because of their sequence homology to the invertebrate gap junction family (innexins), pannexins have been shown mainly to form functional single membrane channels. 2,3 Out of over 100 published papers, less than half a dozen support a gap junction role for pannexins, and these studies are restricted to pannexin overexpression in in vitro systems. [4][5][6][7] On the other hand, all three members of the mammalian pannexin family of tetraspanning membrane proteins (Panx1, Panx2, and Panx3; Figure 1 four transmembrane domains, two extracellular loops, one intracellular loop, and intracellular amino (NH 2 ) and carboxyl (COOH) termini.…”

Section: Introductionmentioning

confidence: 99%

The cellular life of pannexins

Peñuela

Laird

2012

WIREs Membr Transp Signal

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The mammalian pannexin family of channel-forming proteins consisting of Panx1, Panx2, and Panx3 has received considerable attention in the last 10 years given their newly discovered physiological roles in development and disease. Pannexins exhibit diverse subcellular profiles indicating that they may serve distinct roles in cells and tissues of different origin. This complexity in cellular residencies may be rooted in the fact that pannexin genes consist of multiple exons that have led to the identification of several splice variants. Additionally, post-translational modifications, especially N-glycosylation, appear to be important in regulating trafficking and intermixing of pannexin family members increasing the diversity of assembled channels. These long-lived membrane proteins are typically trafficked through the classical secretory pathway before reaching the plasma membrane although Panx2 tends to often be retained in intracellular compartments. Trafficking, stability, and function of pannexins likely enlist the services of an interactome that continues to expand. The research field has been amazed by the fact that Panx1 null mice are generally healthy with distinct phenotypes only being revealed when mutant mice encounter additional stress or have comorbidities. The emerging field of pannexin biology has also begun to explore the relationships and potential cross-talk between pannexin channels and connexin hemichannels. It is imperative to dissect the different constituents of the channels and the molecules that pass through these distinct channel types. Finally, as witnessed in connexin biology throughout the 90s, the field awaits to see if germline mutations in the genes that encode pannexins also cause disease.

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Pannexin channels are not gap junction hemichannels

Cited by 319 publications

References 36 publications

Structural and Functional Similarities of Calcium Homeostasis Modulator 1 (CALHM1) Ion Channel with Connexins, Pannexins, and Innexins*

Structural and Functional Similarities of Calcium Homeostasis Modulator 1 (CALHM1) Ion Channel with Connexins, Pannexins, and Innexins*

Pannexin 1, an ATP Release Channel, Is Activated by Caspase Cleavage of Its Pore-associated C-terminal Autoinhibitory Region

The cellular life of pannexins

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