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

James I Elliott, Annmarie Surprenant, Federica M Marelli-Berg, Joanne C Cooper, Robin L Cassady-Cain, Carol Wooding, Kenneth Linton, Denis R Alexander, Christopher F Higgins

Research output: Contribution to journalArticlepeer-review

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 P2X(7). Changes in PS distribution were shown to modulate several membrane activities: Ca(2+) and Na(+) uptake through the P2X(7) cation channel itself; P2X(7)-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.
Original languageEnglish
Pages (from-to)808-16
Number of pages9
JournalNature Cell Biology
Volume7
Issue number8
DOIs
Publication statusPublished - Aug 2005

Keywords

  • Adenosine Triphosphate
  • Animals
  • Annexin A5
  • Antigens, CD45
  • Apoptosis
  • Biological Transport
  • CD4-Positive T-Lymphocytes
  • Calcium
  • Cell Membrane
  • Cell Movement
  • Cell Survival
  • Drug Resistance, Multiple
  • Ion Channels
  • L-Selectin
  • Lymphocytes
  • Membrane Proteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Knockout
  • Mice, Transgenic
  • Models, Biological
  • P-Glycoprotein
  • Paclitaxel
  • Phosphatidylserines
  • Purinergic P2 Receptor Agonists
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2X7
  • Signal Transduction
  • T-Lymphocyte Subsets

Fingerprint

Dive into the research topics of 'Membrane phosphatidylserine distribution as a non-apoptotic signalling mechanism in lymphocytes'. Together they form a unique fingerprint.

Cite this