Nature Cell Biology 7, 808 - 816 (2005)
Published online: 17 July 2005; | doi:10.1038/ncb1279
Membrane phosphatidylserine distribution as a non-apoptotic signalling mechanism in lymphocytesJames I. Elliott1, Annmarie Surprenant3, Federica M. Marelli-Berg2, Joanne C. Cooper4, Robin L. Cassady-Cain5, Carol Wooding1, Kenneth Linton1, Denis R. Alexander4
& Christopher F. Higgins11
MRC Clinical Sciences Centre, Imperial College, Hammersmith Hospital Campus, Du Cane Rd, London W12 0NN, UK. 2
Department of Immunology, Faculty of Medicine, Imperial College, Hammersmith Hospital Campus, Du Cane Rd, London W12 0NN, UK. 3
Institute of Molecular Physiology, Department of Biomedical Science, Addison Bldg, Western Bank, University of Sheffield, S10 2TN, UK. 4
Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Babraham, Cambridge CB2 4AT, UK. 5
Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
Correspondence should be addressed to James I. Elliott james.elliott@csc.mrc.ac.uk 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.
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