Raft localisation of FcgammaRIIa and efficient signaling are dependent on palmitoylation of cysteine 208.
Ligand-dependent aggregation of FcgammaRIIa initiates multiple biochemical processes including the translocation to detergent resistant membrane domains (DRMs) and receptor tyrosine phosphorylation. Palmitoylation of cysteine residues is considered to be one process that assists in the localisation of proteins to DRMs. Within the juxtamembrane region of FcgammaRIIa there is cysteine residue (C208) that we show to be palmitoylated. Mutation of this cysteine residue results in the disruption of FcgammaRIIa translocation to DRMs as empirically defined by insolubility at high Triton X-100 concentrations. This study also demonstrates that the lack of lipid raft association diminishes FcgammaRIIa signaling as measured by receptor phosphorylation and calcium mobilisation functions suggesting that FcgammaRIIa signaling is partially dependent on lipid rafts.
Barnes
N C
NC
Helen Macpherson Smith Trust Inflammatory Disease Laboratory, The Austin Research Institute, Austin Health, Studley Road, Heidelberg, Vic. 3084, Australia.
Powell
M S
MS
Trist
H M
HM
Gavin
A L
AL
Wines
B D
BD
Hogarth
P M
PM
D000818:Animals; D015703:Antigens, CD / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology*; D020013:Calcium Signaling; D045744:Cell Line, Tumor; D003545:Cysteine / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D021962:Membrane Microdomains / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D017830:Octoxynol / Q000494:pharmacology; D010168:Palmitates / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D017452:Receptors, IgG / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D015703:Antigens, CD; C080568:Fc gamma receptor IIA; D010168:Palmitates; D017452:Receptors, IgG; D014443:Tyrosine; D017830:Octoxynol; D003545:Cysteine