Pannexin 1 channels regulate leukocyte emigration through the venous endothelium during acute inflammation.
Alexander W. Lohman,Igor L. Leskov,Joshua T. Butcher,Scott R. Johnstone,Tara A. Stokes,Daniela Begandt,Leon J. DeLalio,Angela K. Best,Silvia Penuela,Norbert Leitinger,Kodi S. Ravichandran,Karen Y. Stokes,Brant E. Isakson +12 more
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TLDR
It is reported that the ATP-release channel Pannexin1 (Panx1) opens downstream of EC activation by TNF-α, placing Panx1 channels at the centre of cytokine crosstalk with purinergic signalling in the endothelium.Abstract:
Inflammatory cell recruitment to local sites of tissue injury and/or infection is controlled by a plethora of signalling processes influencing cell-to-cell interactions between the vascular endothelial cells (ECs) in post-capillary venules and circulating leukocytes. Recently, ATP-sensitive P2Y purinergic receptors have emerged as downstream regulators of EC activation in vascular inflammation. However, the mechanism(s) regulating cellular ATP release in this response remains elusive. Here we report that the ATP-release channel Pannexin1 (Panx1) opens downstream of EC activation by TNF-α. This process involves activation of type-1 TNF receptors, recruitment of Src family kinases (SFK) and SFK-dependent phosphorylation of Panx1. Using an inducible, EC-specific Panx1 knockout mouse line, we report a previously unidentified role for Panx1 channels in promoting leukocyte adhesion and emigration through the venous wall during acute systemic inflammation, placing Panx1 channels at the centre of cytokine crosstalk with purinergic signalling in the endothelium.read more
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The Cryo-EM Structure of a Pannexin 1 Channel Reveals an Extracellular Gating Mechanism
TL;DR: The structural and functional study establishes the extracellular loops as the unique structural determinants for channel gating and inhibition in Panx1 thereby providing the founding model to study pannexins.
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Connexin and Pannexin Large-Pore Channels in Microcirculation and Neurovascular Coupling Function
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References
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TL;DR: Pannexin‐1, a recently described mammalian protein that functions as a hemichannel when ectopically expressed, is identified as this dye‐uptake pathway and signalling through pannexin•1 is required for processing of caspase‐1 and release of mature IL‐1β induced by P2X7 receptor activation.
Journal ArticleDOI
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TL;DR: Dynamic in vivo imaging revealed a multistep hierarchy of directional cues that guide neutrophil localization to sites of sterile inflammation, and the underlying mechanisms of recruitment of neutrophils into injured tissue.
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