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, FcγRI (CD64), and membrane microdomains. FcγRI 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 FcγRI to predominantly reside within detergent-insoluble buoyant membranes, together with FcRγ-chain, but independent of cross-linking ligand. With the use of confocal imaging, FcγRI was found to co-patch with GM1, a microdomain-enriched glycolipid. Depletion of cellular cholesterol, furthermore, modulated FcγRI-ligand interactions. These data indicated FcγRI to reside within lipid rafts without prior triggering of the receptor.