title: Binding of perforin to membranes is sensitive to lipid spacing and not headgroup.
abstract: When triggered, cytolytic effector cells (cytolytic T-lymphocytes (CTL) and large granular lymphocytes (LGL)) release effector molecules from cytoplasmic granules, including the lytic protein perforin. This protein binds and incorporates into the plasma membrane of target cells, where it aggregates to form pores which cause target cell lysis and death. Phosphorylcholine, the headgroup of the ubiquitous phospholipids phosphatidylcholine (PC) and sphingomyelin, has been proposed as the specific receptor for perforin. We report here that any headgroup specificity is outweighed by phospholipid spacing in determining binding of perforin to liposomes. We also find that the spacing of outer leaflet lipids in a natural bilayer, the plasma membrane of the erythrocyte, influences susceptibility of the cell to perforin-mediated lysis. Finally, we demonstrate that the plasma membrane lipids in CTL are more closely spaced than in target cells, suggesting that lipid spacing contributes to the relative resistance of CTL to perforin-mediated lysis.
authors.affiliation: Molecular and Cell Biology Program, University of Massachusetts, Amherst 01003.
authors.forename: R
authors.initials: R
authors.lastname: Antia
authors.forename: R A
authors.initials: RA
authors.lastname: Schlegel
authors.forename: P
authors.initials: P
authors.lastname: Williamson
mesh_terms: D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D008081:Liposomes / Q000378:metabolism; D008562:Membrane Glycoproteins; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011744:Pyrimidinones; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D008081:Liposomes; D008562:Membrane Glycoproteins; D008563:Membrane Lipids; D008565:Membrane Proteins; D052899:Pore Forming Cytotoxic Proteins; D011744:Pyrimidinones; D054353:Perforin; C003954:merocyanine dye