Cambi Alessandra, de Lange Frank, van Maarseveen Noortje M, Nijhuis Monique, Joosten Ben, van Dijk Erik M H P, de Bakker Bärbel I, Fransen Jack A M, Bovee-Geurts Petra H M, van Leeuwen Frank N, Van Hulst Niek F, Figdor Carl G
Dept. of Tumor Immunology, Nijmegen Center for Molecular Life Sciences, University Medical Center Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, Netherlands.
J Cell Biol. 2004 Jan 5;164(1):145-55. doi: 10.1083/jcb.200306112.
The C-type lectin dendritic cell (DC)-specific intercellular adhesion molecule grabbing non-integrin (DC-SIGN; CD209) facilitates binding and internalization of several viruses, including HIV-1, on DCs, but the underlying mechanism for being such an efficient phagocytic pathogen-recognition receptor is poorly understood. By high resolution electron microscopy, we demonstrate a direct relation between DC-SIGN function as viral receptor and its microlocalization on the plasma membrane. During development of human monocyte-derived DCs, DC-SIGN becomes organized in well-defined microdomains, with an average diameter of 200 nm. Biochemical experiments and confocal microscopy indicate that DC-SIGN microdomains reside within lipid rafts. Finally, we show that the organization of DC-SIGN in microdomains on the plasma membrane is important for binding and internalization of virus particles, suggesting that these multimolecular assemblies of DC-SIGN act as a docking site for pathogens like HIV-1 to invade the host.
C型凝集素树突状细胞（DC）特异性细胞间粘附分子结合非整合素（DC-SIGN；CD209）促进包括HIV-1在内的多种病毒在DC上的结合与内化，但对于其成为如此高效的吞噬性病原体识别受体的潜在机制却知之甚少。通过高分辨率电子显微镜，我们证明了DC-SIGN作为病毒受体的功能与其在质膜上的微定位之间存在直接关系。在人单核细胞衍生DC的发育过程中，DC-SIGN在平均直径为200nm的明确微结构域中组织形成。生化实验和共聚焦显微镜表明，DC-SIGN微结构域存在于脂筏内。最后，我们表明质膜上微结构域中DC-SIGN的组织对于病毒颗粒的结合与内化很重要，这表明DC-SIGN的这些多分子组装体充当了HIV-1等病原体侵入宿主的对接位点。
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