Membrane phosphatidylserine distribution as a non-apoptotic signalling mechanism in lymphocytes

Elliott, JI; Surprenant, A; Marelli-Berg, FM; Cooper, JC; Cassady-Cain, RL; Wooding, C; Linton, K; Alexander, DR; Higgins, CF

Abstract

Phosphatidylserine (PS) exposure is normally associated with apoptosis and the removal of dying cells. We observed that PS is exposed constitutively at high levels on T lymphocytes that express low levels of the transmembrane tyrosine phosphatase CD45RB. CD45 was shown to be a negative regulator of PS translocation in response to various signals, including activation of the ATP receptor P2X7. Changes in PS distribution were shown to modulate several membrane activities: Ca2+ and Na+ uptake through the P2X7 cation channel itself; P2X7-stimulated shedding of the homing receptor CD62L; and reversal of activity of the multidrug transporter P-glycoprotein. The data identify a role for PS distribution changes in signal transduction, rapidly modulating the activities of several membrane proteins. This seems to be an all-or-none effect, coordinating the activity of most or all the molecules of a target protein in each cell. The data also suggest a new approach to circumventing multidrug resistance.

Citation

Elliott, J., Surprenant, A., Marelli-Berg, F., Cooper, J., Cassady-Cain, R., Wooding, C., …Higgins, C. (2005). Membrane phosphatidylserine distribution as a non-apoptotic signalling mechanism in lymphocytes. Nature Cell Biology, 7(8), 808-U76. https://doi.org/10.1038/ncb1279

• Journal Article Type: Article
• Publication Date: Aug 1, 2005
• Deposit Date: May 17, 2007
• Journal: Nature Cell Biology
• Print ISSN: 1465-7392
• Electronic ISSN: 1476-4679
• Publisher: Nature Research
• Peer Reviewed: Peer Reviewed
• Volume: 7
• Issue: 8
• Pages: 808-U76
• DOI: https://doi.org/10.1038/ncb1279
• Public URL: https://durham-repository.worktribe.com/output/1568603