PUBLICATION
Characterization of ATP-gated P2X7 receptors in fish provides new insights into the mechanism of release of the leaderless cytokine interleukin-1β
- Authors
- Lopez-Castejon, G., Young, M.T., Meseguer, J., Surprenant, A., and Mulero, V.
- ID
- ZDB-PUB-060724-2
- Date
- 2007
- Source
- Molecular immunology 44(6): 1286-1299 (Journal)
- Registered Authors
- Keywords
- Fish, Cytokines, Comparative immunology, Phylogeny
- MeSH Terms
-
- Adenosine Triphosphate/physiology*
- Amino Acid Sequence
- Animals
- Cell Line
- Humans
- Interleukin-1beta/chemistry
- Interleukin-1beta/metabolism
- Ion Channel Gating/immunology*
- Molecular Sequence Data
- Protein Sorting Signals/physiology*
- Rats
- Receptors, Purinergic P2/chemistry*
- Receptors, Purinergic P2/genetics
- Receptors, Purinergic P2/physiology*
- Receptors, Purinergic P2X7
- Sea Bream/metabolism*
- Xenopus
- Zebrafish
- PubMed
- 16837047 Full text @ Mol. Immunol.
Citation
Lopez-Castejon, G., Young, M.T., Meseguer, J., Surprenant, A., and Mulero, V. (2007) Characterization of ATP-gated P2X7 receptors in fish provides new insights into the mechanism of release of the leaderless cytokine interleukin-1β. Molecular immunology. 44(6):1286-1299.
Abstract
Mammalian interleukin-1beta (IL-1beta) is produced as a biologically inactive precursor molecule, which is proteolytically cleaved to an active form by IL-1beta-converting enzyme (ICE) after the activation of P2X(7) receptor by extracellular ATP. The mechanism of IL-1beta release in non-mammalian vertebrates is largely unknown, although most of the IL-1beta gene sequences lack a conserved ICE recognition site. Here we have cloned the P2X(7) receptor from the bony fish seabream and compared agonist and antagonist profiles at this and other non-mammalian P2X(7) receptors expressed in HEK cells, as well in seabream SAF-1 cells expressing endogenous P2X(7) receptors. We used this information to further investigate the mechanisms of IL-1beta release induced by mammalian and fish P2X(7) receptors. Despite phosphatidylserine externalization and cell permeabilization in seabream leukocytes after the addition of high BzATP concentrations, IL-1beta remained unprocessed within the cell. However, activation of rat P2X(7) receptors ectopically expressed in HEK293 together with human ICE led to the specific secretion of unprocessed seabream IL-1beta. In contrast, neither seabream nor zebrafish P2X(7) receptors induced the secretion of mammalian or fish IL-1beta when expressed in HEK293, while a chimeric receptor harboring the ATP-binding domain of seabream P2X(7) and the intracellular region of its rat counterpart did so. These findings indicate that P2X(7) receptor-mediated activation of ICE and release of IL-1beta result from different downstream signaling pathways and suggest that although the mechanisms involved in IL-1beta secretion are conserved throughout evolution, distinct inflammatory signals have been selected for the secretion of this cytokine in different vertebrates.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping