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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

Authors

JI Elliott

A Surprenant

FM Marelli-Berg

JC Cooper

RL Cassady-Cain

C Wooding

K Linton

DR Alexander

CF Higgins



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