Elliott, J. I. and Surprenant, A. and Marelli-Berg, F. M. and Cooper, J. C. and Cassady-Cain, R. L. and Wooding, C. and Linton, K. and Alexander, D. R. and Higgins, C. F. (2005) 'Membrane phosphatidylserine distribution as a non-apoptotic signalling mechanism in lymphocytes.', Nature cell biology., 7 (8). 808-U76.
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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|Publisher Web site:||http://dx.doi.org/10.1038/ncb1279|
|Record Created:||17 May 2007|
|Last Modified:||08 Apr 2009 16:31|
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