title: Transmembrane voltage regulates binding of annexin V and lactadherin to cells with exposed phosphatidylserine.
abstract: BACKGROUND
  Cells expose phosphatidylserine during apoptosis. The voltage across the plasma membrane also decreases or disappears during apoptosis, but the physiological significance of this is unknown.
  
  
  RESULTS
  Here we show that transmembrane potential regulates membrane binding of two unrelated proteins that recognize exposed phosphatidylserine on apoptotic cells. In Jurkat T leukemia cells and K562 promyelocytic leukemia cells undergoing apoptosis, extracellular binding of annexin V was increased by decreasing membrane potential in a dose-dependent manner. Studies with phospholipid vesicles showed that the effect was mediated via an increase in binding affinity. The effect was independent of the apoptotic stimulus. The same phenomenon occurred with lactadherin, a structurally unrelated protein that also binds to apoptotic cells via phosphatidylserine and is essential for in vivo clearance of dying cells.
  
  
  CONCLUSIONS
  Alterations in membrane potential regulate the binding of annexin V and lactadherin to cell membranes, and may also influence the membrane binding of other classes of phosphatidylserine-binding proteins.
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, WA 98195-7110, USA. smithc@u.washington.edu
authors.forename: Christina
authors.initials: C
authors.lastname: Smith
authors.forename: Donald F
authors.initials: DF
authors.lastname: Gibson
authors.forename: Jonathan F
authors.initials: JF
authors.lastname: Tait
mesh_terms: D017304:Annexin A5 / Q000737:chemistry / Q000378:metabolism*; D000954:Antigens, Surface / Q000737:chemistry / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology; D002462:Cell Membrane / Q000502:physiology; D003513:Cycloheximide / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D019169:Jurkat Cells; D020014:K562 Cells; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D008894:Milk Proteins / Q000737:chemistry / Q000378:metabolism*; D008956:Models, Chemical; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology; D010718:Phosphatidylserines / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D014466:Ultraviolet Rays
chemical_list: D017304:Annexin A5; D000954:Antigens, Surface; C098942:MFGE8 protein, human; D008894:Milk Proteins; D009467:Neuromuscular Depolarizing Agents; D010718:Phosphatidylserines; D003513:Cycloheximide