title: Imaging of Fas-FasL membrane microdomains during apoptosis in a reconstituted cell-cell junction.
abstract: The Fas death receptor interacts with its ligand FasL and induces apoptosis. The Fas-FasL interaction occurs at the cell-cell interface in vivo, since both proteins are expressed in cell membranes. However, most studies on the Fas signal pathway have been performed in a nonphysiological manner by using soluble molecules (antibody or crosslinked FasL proteins) to stimulate Fas. The Fas-FasL interaction at the cell-cell contact site has only been studied recently, but the information derived from cell-cell interaction studies is still rather limited and not necessarily consistent with the past results obtained by using soluble Fas-stimulatory molecules. Therefore, we develop a novel reconstituted system that mimics the Fas-FasL interaction at cell-cell contact sites for further examination of the physiological Fas-FasL signaling system. By conjugating FasL extracellular domains to planar lipid bilayers, we created a model cell membrane to activate Fas-expressing cells. Using this system, we generated an image of Fas-FasL interactions at the cell-membrane interface at high resolution. We observed that the Fas-FasL interaction between two membranes creates submicron membrane microdomains. Shortly after microdomain formation, the cells exhibit various features of apoptosis. These results suggest that our reconstituted system provides a useful platform to dissect Fas-FasL apoptosis signaling at near physiological conditions.
authors.affiliation: Graduate School of Life Science, Hokkaido University, N10W8, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kaizuka
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Hanagata
mesh_terms: D017209:Apoptosis; D002450:Cell Communication; D053222:Fas Ligand Protein / Q000378:metabolism*; D006801:Humans; D007365:Intercellular Junctions; D019169:Jurkat Cells; D008051:Lipid Bilayers / Q000378:metabolism; D021962:Membrane Microdomains / Q000378:metabolism*; D008954:Models, Biological; D057054:Molecular Imaging / Q000379:methods*; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D053222:Fas Ligand Protein; D008051:Lipid Bilayers; D019014:fas Receptor