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The pannexins: past and present

1 , 2 , 2

Frontiers in Physiology

Frontiers Media S.A.

pannexin, Panx1, Panx2, Panx3, distribution, biochemistry, structure, gating

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      Abstract

      The pannexins (Panxs) are a family of chordate proteins homologous to the invertebrate gap junction forming proteins named innexins. Three distinct Panx paralogs (Panx1, Panx2, and Panx3) are shared among the major vertebrate phyla, but they appear to have suppressed (or even lost) their ability to directly couple adjacent cells. Connecting the intracellular and extracellular compartments is now widely accepted as Panx's primary function, facilitating the passive movement of ions and small molecules along electrochemical gradients. The tissue distribution of the Panxs ranges from pervasive to very restricted, depending on the paralog, and are often cell type-specific and/or developmentally regulated within any given tissue. In recent years, Panxs have been implicated in an assortment of physiological and pathophysiological processes, particularly with respect to ATP signaling and inflammation, and they are now considered to be a major player in extracellular purinergic communication. The following is a comprehensive review of the Panx literature, exploring the historical events leading up to their discovery, outlining our current understanding of their biochemistry, and describing the importance of these proteins in health and disease.

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        Infection of cells by microorganisms activates the inflammatory response. The initial sensing of infection is mediated by innate pattern recognition receptors (PRRs), which include Toll-like receptors, RIG-I-like receptors, NOD-like receptors, and C-type lectin receptors. The intracellular signaling cascades triggered by these PRRs lead to transcriptional expression of inflammatory mediators that coordinate the elimination of pathogens and infected cells. However, aberrant activation of this system leads to immunodeficiency, septic shock, or induction of autoimmunity. In this Review, we discuss the role of PRRs, their signaling pathways, and how they control inflammatory responses. 2010 Elsevier Inc. All rights reserved.
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          Inflammasomes are molecular platforms activated upon cellular infection or stress that trigger the maturation of proinflammatory cytokines such as interleukin-1beta to engage innate immune defenses. Strong associations between dysregulated inflammasome activity and human heritable and acquired inflammatory diseases highlight the importance this pathway in tailoring immune responses. Here, we comprehensively review mechanisms directing normal inflammasome function and its dysregulation in disease. Agonists and activation mechanisms of the NLRP1, NLRP3, IPAF, and AIM2 inflammasomes are discussed. Regulatory mechanisms that potentiate or limit inflammasome activation are examined, as well as emerging links between the inflammasome and pyroptosis and autophagy. 2010 Elsevier Inc. All rights reserved.
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            Author and article information

            Affiliations
            1Genome Technology Branch, Division of Intramural Research, National Human Genome Research Institute, National Institutes of Health Bethesda, MD, USA
            2Department of Cellular and Physiological Science, Life Sciences Institute, University of British Columbia Vancouver, BC, Canada
            Author notes

            Edited by: Georg Zoidl, York University, Canada

            Reviewed by: Georg Zoidl, York University, Canada; Eliana Scemes, Albert Einstein College of Medicine, USA

            *Correspondence: Stephen R. Bond, Genome Technology Branch, Division of Intramural Research, National Human Genome Research Institute, National Institutes of Health, 50 South Drive, Bethesda, MD 20892, USA e-mail: steve.bond@ 123456nih.gov

            This article was submitted to Membrane Physiology and Membrane Biophysics, a section of the journal Frontiers in Physiology.

            Journal
            Front Physiol
            Front Physiol
            Front. Physiol.
            Frontiers in Physiology
            Frontiers Media S.A.
            1664-042X
            19 February 2014
            2014
            : 5
            3928549 10.3389/fphys.2014.00058
            Copyright © 2014 Bond and Naus.

            This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

            Counts
            Figures: 2, Tables: 2, Equations: 0, References: 264, Pages: 24, Words: 24143
            Categories
            Physiology
            Review Article

            Anatomy & Physiology

            gating, structure, biochemistry, distribution, panx3, panx2, panx1, pannexin

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