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Epithelial Membrane Proteins Induce Membrane Blebbing and Interact with the P2X7 Receptor C Terminus

The binding of extracellular ATP to the P2X7 receptor opens an integral cation-permeable channel; it also leads to membrane blebbing and, in certain immune cells, interleukin-1β secretion and eventual death. The latter three effects are unique to the P2X7 receptor; also unique among P2X receptors is...

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Bibliographic Details
Published in:The Journal of biological chemistry 2002-09, Vol.277 (37), p.34017-34023
Main Authors: Wilson, Heather L., Wilson, Stuart A., Surprenant, Annmarie, North, R. Alan
Format: Article
Language:English
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Summary:The binding of extracellular ATP to the P2X7 receptor opens an integral cation-permeable channel; it also leads to membrane blebbing and, in certain immune cells, interleukin-1β secretion and eventual death. The latter three effects are unique to the P2X7 receptor; also unique among P2X receptors is the long intracellular C terminus of the protein. We have shown that the C-terminal domain of the P2X7receptor is responsible for the cell blebbing phenotype. A screen for proteins that associate with the C-terminal domain of the P2X7 receptor and might mediate the blebbing phenotype, identified epithelial membrane protein 2 (EMP-2). The interaction between EMP-2 and P2X7 was confirmed biochemically by co-immunoprecipitation, co-purification, and glutathioneS-transferase pull-down assays, and this interaction was entirely dependent on the C-terminal domain of P2X7. The P2X7 receptor also interacted with the other members of the epithelial membrane protein family (EMP-1, EMP-3, and PMP-22). All four EMPs were found to be expressed in HEK-293 cells and in THP-1 monocytes, which express P2X7 receptors. Interestingly, the constitutive overexpression of any of the EMPs in HEK-293 cells led to cell blebbing, annexin V binding, and cell death, by a caspase-dependent pathway. These findings suggest that the P2X7 C-terminal domain associates with EMPs, and this interaction may mediate some aspects of the downstream signaling following P2X7 receptor activation.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M205120200