Identification of novel proteins involved in P2X7-mediated signaling cascades

High concentration of extracellular ATP acts as a danger signal that is sensed by the P2X7 receptor (P2X7R). This ATP-gated ion channel has been shown to induce multiple metabotropic events such as changes in plasma membrane composition and morphology, ectodomain shedding, activation of lipases, kin...

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Bibliographic Details
Published in:Purinergic signalling 2022-12, Vol.18 (4), p.495-498
Main Author: Sassenbach, Lukas
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - pharmacology
Animals
Biomedical and Life Sciences
Biomedicine
Cancer Research
CD25 antigen
CD4 antigen
CRISPR
Cytolysis
Genomes
Human Physiology
Journal Club
Lymphocyte Activation
Lymphocytes T
Lysis
Membrane composition
Metabotropic receptors
Mice
Molecular modelling
Neurosciences
Pharmacology/Toxicology
Reactive oxygen species
Receptors, Purinergic P2X7
Signal Transduction
T-Lymphocytes
Transcription factors
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Summary:High concentration of extracellular ATP acts as a danger signal that is sensed by the P2X7 receptor (P2X7R). This ATP-gated ion channel has been shown to induce multiple metabotropic events such as changes in plasma membrane composition and morphology, ectodomain shedding, activation of lipases, kinases, and transcription factors as well as cytokine release. The specific signaling pathways and molecular mechanisms remain largely obscure. Using an unbiased genome-scale CRISPR/Cas9 screening approach in a murine T cell line, Ryoden et al. (2022, 2020) identified three proteins involved in P2X7 regulation and signaling: Essential for Reactive Oxygen Species (EROS) is essential for P2X7 folding and maturation, and Xk and Vsp13a are required for P2X7-mediated phosphatidyl serine exposure and cell lysis. They further provide evidence for an interaction of Xk and Vsp13a at the plasma membrane and confirm the role of Xk in ATP-induced cytolysis in primary CD25 + CD4 + T cells from Xk −/− mice.
ISSN:1573-9538
1573-9546
DOI:10.1007/s11302-022-09893-z