UPDATE: Hoorig graduated in early 2008 and will be, sadly, leaving us for bigger and better (?!) things...tears.

DC-SIGN is a C-type lectin receptor highly expressed by dendritic cells (DCs), which are professional antigen-presenting cells. Our interest in this receptor stems from its ability to bind to HIV-1 envelope glycoprotein gp120 with high affinity. It is thought that DC-SIGN mediates the transfer of HIV from dendritic cells to permissive Tcells. This has led to the hypothesis that DC-SIGN may serve as a conduit for the transfer of HIV from the peripheral mucosa to secondary lymphoid organs.

As a type II integral membrane protein, DC-SIGN has an extracellular C-terminal carbohydrate recognition domain, a hydrophobic transmembrane domain, and an N-terminal cytoplasmic domain (CD). Analysis of the cytoplasmic domain of DC-SIGN reveals three putative internalization and sorting motifs that may play a role in receptor endocytosis and trafficking. These include a dileucine motif (LL), a triacidic cluster (EEE), and a tyrosine-based endocytic motif (YKSL). The function of some of these CD motifs in DC-SIGN has been characterized to some extent, but the kinetics of DC-SIGN internalization, and the specific contribution that these CD motifs make to the process of DC-SIGN-mediated viral transfer have not been examined.

By generating a panel of DC-SIGN CD mutants, we can study the relative contribution of each motif in DC-SIGN endocytosis and recycling. Since these motifs may also function in sorting and trafficking, immunofluorescence analysis can be utilized to determine whether each mutant colocalizes with various intracellular compartments such as endosomes, lysosomes, or the trans-Golgi network. By using multiple biochemical and cell biological tools, we can probe the endocytic behavior of DC-SIGN in transiently transfected cells as well as in primary dendritic cells, and this will yield valuable information about the nature of this immune system lectin.

If interested, please take a look at the following journal papers on this work:

DC-SIGN review:

Su SV, Gurney KB, Lee B. (2003). Sugar and spice:
viral envelope-DC-SIGN interactions in HIV
pathogenesis. Curr HIV Res 1:87-99

Internalization/Sorting Signals review:

Bonifacino JS, Traub LM. (2003). Signals for sorting
of transmembrane proteins to endosomes and lysosomes.
Annu Rev Biochem 72:395-447

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