DC-SIGN and Influenza Hemagglutinin Dynamics in Plasma Membrane Microdomains Are Markedly Different
DC-SIGN and Influenza Hemagglutinin Dynamics in Plasma Membrane Microdomains Are Markedly Different
复制标题
DOI：
10.1016/j.bpj.2011.04.044
复制
发表时间：
2011-06-08
影响因子：
3.4
通讯作者：
Jacobson, Ken
中科院分区：
文献类型：
--
作者：
Itano, Michelle S.;Neumann, Aaron K.;Jacobson, Ken
DC-SIGN是一种钙离子依赖性跨膜凝集素，主要分布于树突状细胞质膜上的微区。这些微结构域结合多种病原体，并促进它们的摄取用于随后的抗原呈递。在这项研究中，DC-SIGN动力学在微区进行了探索与几种荧光显微镜方法，并与流感血凝素（HA），这也是质膜微区中发现的动力学进行了比较。荧光成像表明，DC-SIGN微区可能含有其他C型凝集素，DC-SIGN胞质区是不需要微区的形成。光漂白测量后的荧光恢复表明，无论是全长还是胞质截断DC-SIGN微域明显交换与其他微域和膜周围的类似分子，而HA微域交换几乎完全。线扫描荧光相关光谱表明，DC-SIGN基本上检测不到的横向流动性，但HA在各自的域内的可观的流动性。单粒子跟踪与定义价量子点证实，HA具有显着的流动性内的微区，而DC-SIGN没有。相比之下，光漂白后的荧光恢复表明，内小叶脂质能够移动通过DC-SIGN微域。DC-SIGN微结构域令人惊讶的稳定性可能反映了通过提供高亲合力平台和/或通过防止快速微结构域内吞来增强病原体摄取的结构特征。
DC-SIGN, a Ca(2+)-dependent transmembrane lectin, is found assembled in microdomains on the plasma membranes of dendritic cells. These microdomains bind a large variety of pathogens and facilitate their uptake for subsequent antigen presentation. In this study, DC-SIGN dynamics in microdomains were explored with several fluorescence microscopy methods and compared with dynamics for influenza hemagglutinin (HA), which is also found in plasma membrane microdomains. Fluorescence imaging indicated that DC-SIGN microdomains may contain other C-type lectins and that the DC-SIGN cytoplasmic region is not required for microdomain formation. Fluorescence recovery after photobleaching measurements showed that neither full-length nor cytoplasmically truncated DC-SIGN in microdomains appreciably exchanged with like molecules in other microdomains and the membrane surround, whereas HA in microdomains exchanged almost completely. Line-scan fluorescence correlation spectroscopy indicated an essentially undetectable lateral mobility for DC-SIGN but an appreciable mobility for HA within their respective domains. Single-particle tracking with defined-valency quantum dots confirmed that HA has significant mobility within microdomains, whereas DC-SIGN does not. By contrast, fluorescence recovery after photobleaching indicated that inner leaflet lipids are able to move through DC-SIGN microdomains. The surprising stability of DC-SIGN microdomains may reflect structural features that enhance pathogen uptake either by providing high-avidity platforms and/or by protecting against rapid microdomain endocytosis.