Research Highlights

Siglecs: Different destinations reflect their roles

Confocal microscopy picture (overlay) of CD22 carrying a sialylated probe (green) to the early endosome/recycling compartments marked by the transferrin receptor (red/yellow). Copyright © 2007, American Society for Microbiology

The sialic acid-binding immunoglobulin-like lectin (Siglec) transmembrane receptors are known to play important roles in signal transduction (see here). The Siglec CD22 is a modulator of B-cell receptor (BCR) function and activation. In contrast to CD22, CD33-related Siglecs are expressed on cells of the innate immune system such as eosinophils and are involved in mediating the allergic response. Since more than 20 microorganisms express sialic acid on their surface, the CD33-related Siglec-F might have an additional role in innate immunity. In Molecular and Cellular Biology, Tateno et al. now find that CD22 and Siglec-F follow different endocytic pathways that evince their distinct cellular functions.

Previous studies have found that CD22 endocytosis follows the clathrin-dependent pathway that also internalizes the BCR. Upon antibody ligation, Siglec-F expressed on Chinese hamster ovary cells was internalized into the cell, but intracellular Siglec-F and clathrin did not co-localize. Expression of a dominant-negative dynamin-1 mutant also did not abolish Siglec-F internalization. These results suggest that Siglec-F endocytosis is clathrin- and dynamin independent.

Next, Tateno et al. examined the subcellular localization of internalized CD22 and found that CD22 co-localized with the transferrin receptor in early endosomes. In contrast, Siglec-F co-localized with lysosomal markers, indicating that Siglec-F is sorted to the lysosomal compartment. A biological function of Siglec-F endocytosis in protective immune function became clear when Tateno et al. discovered that sialic-acid containing ligands of Siglec-F were also sorted to the lysosomal compartment. Moreover, Neisseria meningitidis bacteria that possess a sialylated lipooligosaccharide bound to Siglec-F, after which the receptor-bacterium complex was internalized into the cell.

Taken together, the results of this study clearly demonstrate that these two important Siglecs exploit two fundamentally different endocytic pathways. The clathrin-dependent pathway that CD22 follows may promote its recycling after BCR activation, while the lysosomal targeting of Siglec-F following its attachment to sialic acid-expressing pathogens attests to a protective role in the immune system, as bound pathogens can be destroyed in the lysosome. Thus, further exploration of the CD33-related Siglecs' role in innate immunity is worthy of future studies.

Author: Mirko von Elstermann