Within the cell membrane, many receptors reside that mediate signal transduction into the cell. Advanced microscopy techniques have unravelled how receptor nanoscale organization and lateral mobility contribute to modulate signal transduction.
In a recent publication in Proc Nat Acad Sci USA, Alessandra Cambi (photo left) and Sonja Buschow (photo right), Dept. of Tumor Immunology together with colleagues from the Institute of Photonic Sciences (Barcelona, Spain) demonstrated a novel mechanism of plasma embrane lateral organization based on glycan-protein interactions.
Cambi and colleagues revealed that besides protein-protein and protein-lipid interactions, glycans can also pattern the cell membrane modulating receptor mobility and favoring interactions with specific downstream effectors. Glycans are fundamental cellular components present in the cell membrane as glycoproteins or glycolipids. Glycan-binding proteins are often multivalent, thus cross-linking glycomolecules into higher-order aggregates, creating a cell membrane glycan-based lattice. By concentrating or excluding specific glycoproteins or glycolipids, this glycan-based lattice can organize the plasma membrane into specialized areas with unique functions. Here, the authors applied superresolution nanoscopy and developed a dedicated dual-color single-molecule spatio-dynamic exploration approach to visualize for the first time the impact of glycan-based interactions on the spatiotemporal organization and clathrin interaction of DC-SIGN, a glycosylated transmembrane receptor involved in pathogen recognition and uptake. This glycan-based micropatterning cages mobile DC-SIGN nanodomains into clathrin-enriched regions, thereby increasing clathrin-receptor interactions and influencing endocytosis of receptor-bound virus-like particles. Given its importance in supporting primary immune responses such as pathogen recognition and uptake on dendritic cells, DC-SIGN is an interesting candidate to specifically target nanoparticles carrying anti-tumor signals to activate dendritic cells. Knowledge of fundamental cellular processes at the nanoscale can contribute to foster novel strategies in nanomedicine.
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