PANX1

Official Full Name

pannexin 1

Organism

Homo sapiens

GeneID

24145

Background

The protein encoded by this gene belongs to the innexin family. Innexin family members are the structural components of gap junctions. This protein and pannexin 2 are abundantly expressed in central nerve system (CNS) and are coexpressed in various neuronal populations. Studies in Xenopus oocytes suggest that this protein alone and in combination with pannexin 2 may form cell type-specific gap junctions with distinct properties. [provided by RefSeq, Jul 2008]

Synonyms

PX1; MRS1; OOMD7; OZEMA7; UNQ2529;

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Detailed Information

New mechanistic insights of PANX1 in inflammation heats up for its implication for injury and infection

Upregulation of pro-inflammatory cytokines, such as interleukin (IL)-1 beta, is the key for tumor necrosis factor (TNF)-alpha triggered inflammation in endothelial cells, while there is still unsatisfied understanding of molecular mechanisms driving their production, processing, or release. Pannexin 1 was recently implicated to be an intermediary of the TNF-alpha/IL-1beta inflammatory pathway in the human umbilical vein endothelial cell (HUVEC) line. Besides the role as a nucleotide and metabolite channel of PANX1 channel, its permeability for ions of various sizes and charges has also been suggested in previous work. The revelation of its strategically placed positive residues in the recent structural reports detailing PANX1 subunit and channel composition may imply its preference towards passing negatively charged molecules, such as Cl^- and ATP. In the subsequent studies also revealed that the purported tunnels are additionally lined with a set if negatively charged amino acids (aspartate and glutamate), which could facilitate cation or Ca²⁺ transport. This put forward the possibility that various possible open configurations in response to different stimuli may be the result of preference towards supporting alternate permeability to anions or cations. Another possibility may be to account for indirect regulation of Ca²⁺ influx by PANX1, for example by modulating the activity of a Ca²⁺ transporter, exchange, or channel. The crosstalk of PANX1 and NMDAR, which is also known as N-methyl-D-aspartate receptors, present and functional on peripheral endothelial cells, has also been suggested to be involved in the current context.

In peripheral and nervous system pathologies, PANX1-mediated inflammatory signaling, such as the release of ATP and other nucleotides, inflammasome activation and cytokine release, have some implications. IL1B transcription up-regulated by PANX1 implicated in many of these pathologies may represent a potential therapeutic target. Those exciting new findings about the role of PANX1 in inflammation may connect it to TNF-alpha and NF-κB，thus laying the groundwork for unraveling the complexities of inflammatory disease pathogenesis and treatment in endothelial cells as well as other cells expressing PANX1.

Role of PANX1 channels in neuroinflammation

In neurological diseases, such as Alzheimer's disease, multiple sclerosis, neuropathic pain, and brain trauma, neuroinflammation is a major component of central nervous system (CNS) injuries. Release of pro-inflammatory cytokines and chemokines at the damage sites can be initiated by activation of innate immune cells, for the functionality alteration of nearby tissues and mediation of leukocytes recruitment to the injury site. ATP is a molecule released for inflammation response trigger and serves as a chemotactic and endogenous danger signal, and extracellular ATP activates multiple purinergic receptors that have been shown to promote neuroinflammation in a variety of CNS diseases. PANX1 channels may work as the principal conduits of ATP release from dying cells and innate immune cells in the brain.

Figure 1. Panx1 deficiency protects mouse kindneys from ischemia-reperfusion injury (IRI). (Jakub Jankowski, et al. 2018)

References:

Jankowski J, Perry H M, Medina C B, et al. Epithelial and endothelial pannexin1 channels mediate AKI[J]. Journal of the American Society of Nephrology, 2018, 29(7): 1887-1899.
Arias J C S, Wicki-Stordeur L E, Candlish R C, et al. PANX1 in inflammation heats up: New mechanistic insights with implications for injury and infection. Cell Calcium, 2020, 90: 102253.
Seo J H, Dalal M S, Contreras J E. Pannexin-1 channels as mediators of neuroinflammation. International journal of molecular sciences, 2021, 22(10): 5189.

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