FcγRI (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, Fc gamma RI (CD64), and membrane microdomains. FcyRI is a 72 kDa type I glycoprotein that can mediate phagocytosis of opsonized pathogens, but can also effectively capture small immune complexes, and facilitates antigen presentation. We found Fc gamma RI to predominantly reside within detergent-insoluble buoyant membranes, together with FcR gamma-chain, but independent of cross-linking ligand. With the use of confocal imaging, Fc gamma RI was found to co-patch with GM1, a microdomain-enriched glycolipid. Depletion of cellular cholesterol, furthermore, modulated Fc gamma RI-ligand interactions. These data indicated Fc gamma RI to reside within lipid rafts without prior triggering of the receptor. (C) 2008 Elsevier B.V. All rights reserved.