A cell permeant peptide containing the cytoplasmic tail sequence of Fc receptor type IIA reduces calcium signaling and phagolysosome formation in neutrophils.
Receptors for the Fc domain of IgG mediate target recognition, signal transduction, and effector functions including antibody-dependent cytolysis, phagocytosis, and phagolysosome formation. To better understand FcR-mediated functions and to identify potential therapeutic strategies, we employed cell-penetrating ("Trojan") peptides to deliver "wild-type" (LTL) or modified (AAA) FcgammaRIIA tail sequences to the neutrophil's cytoplasm. The Trojan-LTL peptide appeared to label the endoplasmic reticulum whereas the Trojan-AAA peptide distributed throughout the cytoplasm. The Trojan-LTL peptide, but not the Trojan-AAA peptide, decreased Ca(2+) signaling at the phagosome and reduced phagolysosome formation. These studies suggest that FcgammaRIIA's tail can act as a peptide decoy thereby blunting FcgammaRIIA-mediated processes, which, in turn, suggests a possible route in managing inflammatory tissue damage.
Clark
Andrea J
AJ
Department of Ophthalmology and Visual Sciences, The University of Michigan Medical School, Ann Arbor, 48105, USA.
Petty
Howard R
HR
D000595:Amino Acid Sequence; D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D002463:Cell Membrane Permeability / Q000502:physiology*; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D008561:Membrane Fusion; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism*; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D010588:Phagosomes / Q000378:metabolism*; D017452:Receptors, IgG / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism
C080568:Fc gamma receptor IIA; D010455:Peptides; D017452:Receptors, IgG