Release of IL-6 from dendritic cells

Recently Daniëlle Verboogen, Geert van den Bogaart and colleagues published an article in Elife entitled: Fluorescence lifetime imaging microscopy reveals rerouting of SNARE trafficking driving dendritic cell activation.

Publication in Elife

Many processes in living cells involve membranes coming together and fusing. For example, white blood cells known as dendritic cells rely on membrane fusion to fight off infections. When a dendritic cell detects a bacterial infection, it releases signaling molecules called cytokines to recruit other immune cells that help to eliminate the bacteria. The cytokines are contained in membrane-bound packages inside the cell, called vesicles, and are transported outside when these vesicles fuse with the membrane that surrounds the dendritic cell. Proteins called SNAREs drive the fusion of a cell’s membranes. These proteins, which are found on both membranes that will fuse, entwine to form a tight complex that pulls the membranes together. Mammals have over 30 different SNARE proteins, and many scientists believe that specific transport routes within cells use distinct pairs of SNAREs. However, to date, it has been difficult to assign specific pairs of SNAREs to specific transport routes with existing techniques.

Verboogen et al. have now engineered human dendritic cells to add labels onto their SNAREs that fluoresce if the proteins interact. This approach meant that the interactions could be tracked via a microscope. The experiments showed that exposing dendritic cells to a bacterial compound that stimulates the release of cytokines caused two SNARE proteins called syntaxin 4 and VAMP3 to interact more at the cell membrane. This indicates that syntaxin 4 and VAMP3 are important for the release of cytokines from these cells. This finding was supported by an additional experiment in which Verboogen et al. switched off the gene for VAMP3 in the dendritic cells and found that this reduced the amount of cytokines that were released.

This new microscope-based approach will be useful for identifying the specific pairs of SNARE proteins that are needed for the release and transport of molecules – like hormones and enzymes – that are important in health and disease.