Pannexin1 as mediator of inflammation and cell death

• Published in: Biochimica et biophysica acta Vol. 1864; no. 1; pp. 51 - 61
• Main Authors: Crespo Yanguas, Sara, Willebrords, Joost, Johnstone, Scott R., Maes, Michaël, Decrock, Elke, De Bock, Marijke, Leybaert, Luc, Cogliati, Bruno, Vinken, Mathieu
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2017
• Subjects: Animals; Apoptosis; Autophagy; Cell Death - genetics; Cell Death - immunology; Cell Membrane - immunology; Cell Membrane - metabolism; Cell Movement; Connexins - chemistry; Connexins - genetics; Connexins - immunology; Cytokines - biosynthesis; Cytokines - immunology; Cytosol - immunology; Cytosol - metabolism; Gene Expression Regulation; Humans; Inflammasomes - immunology; Inflammasomes - metabolism; Inflammation; Inflammation - genetics; Inflammation - immunology; Inflammation - pathology; Leukocytes - immunology; Leukocytes - pathology; Nerve Tissue Proteins - chemistry; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - immunology; Pannexin; Pyroptosis; Signal Transduction; TNFα; NLRC4; IL1α/1β/2/17/18; Autophagy; LPS; CARD; TLR(s); UTP; ASC; NF-κB; Cx; NLR; PAMP(s); Pyroptosis; [Ca2+]i; Pannexin; NLRP1/3; DAMP(s); Inflammation; CT; HIV; TCR(s); ATP; Panx; Apoptosis
• ISSN: 0167-4889; 0006-3002; 1879-2596; 1878-2434
• DOI: 10.1016/j.bbamcr.2016.10.006

Pannexins form channels at the plasma membrane surface that establish a pathway for communication between the cytosol of individual cells and their extracellular environment. By doing so, pannexin signaling dictates several physiological functions, but equally underlies a number of pathological processes. Indeed, pannexin channels drive inflammation by assisting in the activation of inflammasomes, the release of pro-inflammatory cytokines, and the activation and migration of leukocytes. Furthermore, these cellular pores facilitate cell death, including apoptosis, pyroptosis and autophagy. The present paper reviews the roles of pannexin channels in inflammation and cell death. In a first part, a state-of-the-art overview of pannexin channel structure, regulation and function is provided. In a second part, the mechanisms behind their involvement in inflammation and cell death are discussed. •Pannexin1 channels permeate ions and molecules in the size range of 1.5kDa. Pannexin1 channels are identified as ATP release channels as well as anion selective-channels.•Pannexin1 channels drive inflammation by assisting in the activation of inflammasomes, the release of pro-inflammatory cytokines, and the activation and migration of leukocytes.•Pannexin1 channels facilitate cell death, including apoptosis, pyroptosis and autophagy.•Pannexin1 channels inhibition or activation is an attractive potential therapeutic target in a variety of diseases.