Loss of function of a lupus-associated FcgammaRIIb polymorphism through exclusion from lipid rafts.
Dysfunction of receptors for IgG (FcgammaRs) has been thought to be involved in the pathogenesis of systemic lupus erythematosus (SLE). We show that a recently described SLE-associated polymorphism of FcgammaRIIb (FcgammaRIIbT(232)), encoding a single transmembrane amino acid substitution, is functionally impaired. FcgammaRIIbT(232) is unable to inhibit activatory receptors because it is excluded from sphingolipid rafts, resulting in the unopposed proinflammatory signaling thought to promote SLE.
Floto
R Andres
RA
Cambridge Institute for Medical Research and Department of Medicine, University of Cambridge, Cambridge CB2 2XY, UK. arf27@cam.ac.uk
Clatworthy
Menna R
MR
Heilbronn
Karen R
KR
Rosner
Dalya R
DR
MacAry
Paul A
PA
Rankin
Angela
A
Lehner
Paul J
PJ
Ouwehand
Willem H
WH
Allen
Janet M
JM
Watkins
Nicholas A
NA
Smith
Kenneth G C
KG
D019943:Amino Acid Substitution; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism*; D001402:B-Lymphocytes / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008264:Macrophages / Q000502:physiology; D021962:Membrane Microdomains / Q000378:metabolism*; D011110:Polymorphism, Genetic; D017452:Receptors, IgG / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D020298:U937 Cells
D015703:Antigens, CD; C080571:Fc gamma receptor IIB; D017452:Receptors, IgG