Beekman Jeffrey M, van der Linden Joke A, van de Winkel Jan G J, Leusen Jeanette H W
Immunotherapy Laboratory, Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
Immunol Lett. 2008 Mar 15;116(2):149-55. doi: 10.1016/j.imlet.2007.12.003. Epub 2008 Jan 7.
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.
细胞膜含有被称为“脂筏”或去污剂不溶性微区（DRM）的微区，富含胆固醇和鞘脂。DRM在许多细胞过程中发挥重要作用，包括信号转导、细胞骨架组织和病原体进入。许多受体，如T细胞受体、B细胞受体和IgE受体，已被证明存在于DRM中。这些受体中的大多数依赖多价配体相互作用与这些微区结合。我们在此研究高亲和力IgG受体FcγRI（CD64）与膜微区之间的关联。FcγRI是一种72kDa的I型糖蛋白，可介导调理素化病原体的吞噬作用，但也能有效捕获小免疫复合物，并促进抗原呈递。我们发现FcγRI主要存在于去污剂不溶性浮力膜中，与FcRγ链一起，但与交联配体无关。通过共聚焦成像，发现FcγRI与GM1（一种富含微区的糖脂）共斑。此外，细胞胆固醇的消耗调节了FcγRI-配体相互作用。这些数据表明FcγRI在没有预先触发受体的情况下存在于脂筏中。
