FcgammaRI (CD64) resides constitutively in lipid rafts.
Cellular membranes contain microdomains known as 'lipid rafts' or detergent-insoluble microdomains (DRM), enriched in cholesterol and sphingolipids. DRM can play an important role in many cellular processes, including signal transduction, cytoskeletal organization, and pathogen entry. Many receptors like T cell receptors, B cell receptors and IgE receptors have been shown to reside in DRM. The majority of these receptors depend on multivalent ligand interaction to associate with these microdomains. We, here, study association between the high affinity IgG receptor, FcgammaRI (CD64), and membrane microdomains. FcgammaRI is a 72kDa type I glycoprotein that can mediate phagocytosis of opsonized pathogens, but can also effectively capture small immune complexes, and facilitates antigen presentation. We found FcgammaRI to predominantly reside within detergent-insoluble buoyant membranes, together with FcRgamma-chain, but independent of cross-linking ligand. With the use of confocal imaging, FcgammaRI was found to co-patch with GM1, a microdomain-enriched glycolipid. Depletion of cellular cholesterol, furthermore, modulated FcgammaRI-ligand interactions. These data indicated FcgammaRI to reside within lipid rafts without prior triggering of the receptor.
Beekman
Jeffrey M
JM
Immunotherapy Laboratory, Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
van der Linden
Joke A
JA
van de Winkel
Jan G J
JG
Leusen
Jeanette H W
JH
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D002784:Cholesterol / Q000172:deficiency / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000166:cytology; D021962:Membrane Microdomains / Q000737:chemistry* / Q000378:metabolism*; D051379:Mice; D017452:Receptors, IgG / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D049128:Sphingolipid Activator Proteins / Q000276:immunology
C489017:FCGR1A protein, human; D017452:Receptors, IgG; D049128:Sphingolipid Activator Proteins; D002784:Cholesterol