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© The Rockefeller University Press, 0021-9525/1997//1209 $5.00
The Journal of Cell Biology, Volume 139, Number 5, , 1997 1209-1217

Article

Role for a Glycan Phosphoinositol Anchor in Fc{gamma} Receptor Synergy



Jennifer M. Green*, Alan D. Schreiber{ddagger}, and Eric J. Brown*

* Division of Infectious Diseases, Washington University, School of Medicine, St. Louis, Missouri 63110; and {ddagger} Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104

While many cell types express receptors for the Fc domain of IgG (Fc{gamma}R), only primate polymorphonuclear neutrophils (PMN) express an Fc{gamma}R linked to the membrane via a glycan phosphoinositol (GPI) anchor. Previous studies have demonstrated that this GPI-linked Fc{gamma}R (Fc{gamma}RIIIB) cooperates with the transmembrane Fc{gamma}R (Fc{gamma}RIIA) to mediate many of the functional effects of immune complex binding. To determine the role of the GPI anchor in Fc{gamma} receptor synergy, we have developed a model system in Jurkat T cells, which lack endogenously expressed Fc{gamma} receptors. Jurkat T cells were stably transfected with cDNA encoding Fc{gamma}RIIA and/or Fc{gamma}RIIIB. Cocrosslinking the two receptors produced a synergistic rise in intracytoplasmic calcium ([Ca2+]i) to levels not reached by stimulation of either Fc{gamma}RIIA or Fc{gamma}RIIIB alone. Synergy was achieved by prolonged entry of extracellular Ca2+. Cocrosslinking Fc{gamma}RIIA with CD59 or CD48, two other GPI-linked proteins on Jurkat T cells also led to a synergistic [Ca2+]i rise, as did crosslinking CD59 with Fc{gamma}RIIA on PMN, suggesting that interactions between the extracellular domains of the two Fc{gamma} receptors are not required for synergy. Replacement of the GPI anchor of Fc{gamma}RIIIB with a transmembrane anchor abolished synergy. In addition, tyrosine to phenylalanine substitutions in the immunoreceptor tyrosine-based activation motif (ITAM) of the Fc{gamma}RIIA cytoplasmic tail abolished synergy. While the ITAM of Fc{gamma}RIIA was required for the increase in [Ca2+]i, tyrosine phosphorylation of crosslinked Fc{gamma}RIIA was diminished when cocrosslinked with Fc{gamma}RIIIB. These data demonstrate that Fc{gamma}RIIA association with GPI-linked proteins facilitates Fc{gamma}R signal transduction and suggest that this may be a physiologically significant role for the unusual GPI-anchored Fc{gamma}R of human PMN.

Abbreviations used in this paper: [Ca2+]i, intracytoplasmic Ca2+ concentration; GPI, glycan phosphoinositol; ITAM, immunoreceptor tyrosine-based activation motif; PLC, phospholipase C; PMN, polymorphonuclear neutrophils.

Address all correspondence to Dr. Eric J. Brown, Division of Infectious Diseases, Washington University School of Medicine, 660 S. Euclid Ave., Box 8051, St. Louis, MO 63110. Tel.: (314)362-2125. Fax: (314) 362-9230. E-mail: ebrown{at}id.wustl.edu


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