Lipid metabolism modulation by the P2X7 receptor in the immune system and during the course of infection: new insights into the old view

Abstract

For decades, scientists have described numerous protein pathways and functions. Much of a protein's function depends on its interactions with different partners, and those partners can change depending on the cell type or system. The P2X7 receptor (P2X7R) is one such multifunctional protein that is related to multiple partners and signaling pathways. The relationship between P2X7R and different enzymes involved in lipid metabolism represents a relatively new field in P2X7R research. This field of research began in epithelial cells and currently includes immune and nervous cells. The P2X7R-lipid metabolism pathway is related to many biological functions of P2X7R, such as cell death and pathogen clearance, and this signaling pathway may be involved in many functions that are dependent on bioactive lipids. In the present review, we will attempt to summarize data related to the P2X7R-lipid metabolism pathway, focusing on signaling pathways and their biological relevance to the immune system and infection.

Insights into the Molecular Mechanisms Underlying Mammalian P2X7 Receptor Functions and Contributions in Diseases, Revealed by Structural Modeling and Single Nucleotide Polymorphisms

“…Certainly one should bear in mind that interpretations based on the current crystal structures of the zebrafish P2X4.1R need to exercise cautions as the missing cytosolic N- and C-terminal domains may significantly alter the conformational changes and in particular the movements of the transmembrane domains during receptor activation. No doubt, the structures of a full-length mammalian P2X7R in the closed and ATP-bound open states are required to provide a mechanistic insight into the receptor functions, and particularly the role of the P2X7R specific C-terminal domain (Costa-Junior et al, 2011) and residues in this domain in receptor facilitation and large pore formation (Jiang et al, 2005; Young et al, 2007; Roger et al, 2008, 2010a; Sorge et al, 2012; Xu et al, 2012). The human P2RX7 gene is highly rich in NS-SNPs, and characterizations of the NS-SNP mutations identified in various disease conditions have revealed additional molecular determinants for the human P2X7R functions and, more importantly, have provided new insights into disease mechanisms.…”

P2X7 receptor‐stimulation causes feverviaPGE2 and IL‐1β release

“…Different previous studies suggest that P2 receptors, in particular P2X7R, couple to the release of different autacoids (23–28), and P2 receptor inhibition reduces fever induced by lipopolysaccharide (LPS) in rats (29). Here, we investigate the specific role of P2X7R in PG generation during inflammation and its relevance to the febrile response.…”

Purinergic receptor X7 mediates leptin induced GLUT4 function in stellate cells in nonalcoholic steatohepatitis

“…The P2X7r-lipid metabolism pathway is related to many biological functions of P2X7R, such as cell death and pathogen clearance [35]. This signaling pathway may be involved in many functions that are dependent on bioactive lipids, activation of the different cellular signaling pathways that may mimic insulin signaling and provide an explanation to the differential behavior of stellate cell glucose transport and proliferative responses even in a state of profound insulin resistance [36]. …”