Abstract
DC-SIGN (a single-pass transmembrane protein and C-type lectin) is a major receptor for a variety of pathogens on human dendritic cells including dengue virus (DENV), which has become a global health threat. DENV binds to cell-surface DC-SIGN and the virus/receptor complexes migrate to clathrin-coated pits where the complexes are endocytosed; during subsequent processing, the viral genome is released for replication. DC-SIGN exists on cellular plasma membranes in nanoclusters that may themselves be clustered on longer length scales that appear as microdomains in wide-field and confocal fluorescence microscopy. We have investigated the dynamic structure of these clusters using fluorescence and super-resolution imaging in addition to large-scale single particle tracking. While clusters themselves can be laterally mobile there appears to be little mobility of DC-SIGN within clusters or exchange of DC-SIGN between the clusters and the surroundings. We end this account with some outstanding issues that remain to be addressed with respect to the composition and architecture of DC-SIGN domains and some highly unusual aspects of their lateral mobility on the cell surface that may accompany and perhaps facilitate DENV infection.
One of us (KJ) was profoundly influenced by his interactions with Professor Gregorio Weber who is rightfully the father of fluorescence in biochemistry and molecular and cell biology. Gregorio served as the outside reader on KJ’s Ph.D. thesis that described the fluorescence polarization of perylene in lipid bilayer vesicles as a measure of membrane fluidity. KJ and his young family subsequently traveled to Urbana-Champaign in the summer of 1972 where he worked in the Weber laboratory at the University of Illinois interacting with the Professor and a number of people in the lab at that time, including two graduate students, Dave Jameson and Joe Lakowicz, and two postdoctoral fellows, Dick Spencer and George Mitchell. The summer in Urbana was also productive in that phase fluorimetry was used to measure the rotation of lysozyme bound to acidic phospholipid vesicles for the first time. For KJ and his family, it was a delightful experience, the benefits of which carry forward to today.
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Acknowledgements
This work was supported by NIH grant GM40402 (K.J. & N.L.T.) and RO1-AI107731 (A.M.dS.).
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Jacobson, K., Betts, L., Liu, P., Ridilla, M., de Silva, A., Thompson, N.L. (2016). Plasma Membrane DC-SIGN Clusters and Their Lateral Transport: Role in the Cellular Entry of Dengue Virus. In: Jameson, D. (eds) Perspectives on Fluorescence. Springer Series on Fluorescence, vol 17. Springer, Cham. https://doi.org/10.1007/4243_2016_2
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DOI: https://doi.org/10.1007/4243_2016_2
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