Discovery of a Novel Cell Adhesion Mechanism

In a process essential to the immune system’s response to infection, dendritic cells responsible for identifying pathogens communicate with the T-cells that destroy the infectious agents.

To achieve this, the dendritic cells must be correctly activated and migrate to the lymph nodes where they must adhere firmly to T-cells.

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These processes are, to a large degree, regulated by the integrin lymphocyte-associated antigen-1 (LFA-1).  Earlier studies reported that stable adhesion involved lipid rafts that organize assemblies of cell membrane proteins, including glycosylphosphatidylinositol (GPI) anchored proteins. There has, however, been considerable debate about the existence of these rafts because, owing to their very small size (on the nanometric scale), they could not be observed and their function in the adhesion process was poorly understood.

Image: integrin LFA-1 (red spots) and GPI-anchored proteins (green spots). Cell membrane of the immune system.

A team of researchers in the BioNanoPhotonics group led by María García-Parajo in the Institute of Bioengineering of Catalonia (IBEC) has managed to observe these lipid rafts and has discovered that in the process of cell adhesion they are organized around GPI-anchored proteins and close to LFA-1. The proteins activate LFA-1 and assist throughout the whole process of immune cell adhesion and migration.

These results were obtained using a superresolution optical technique called near-field scanning optical microscopy (NSOM), which makes it possible to work at the nanoscale level. The IBEC team adapted thetechnique to work with biological samples, cells, and biological processes in their natural state. The results have been published in Proceedings of the National Academy of Sciences (PNAS), and the article is available online.

The mechanisms controlling protein organization and cell-cell interaction in the immune system have implications for a large number of autoimmune diseases and allergies, as well as for the rapid transmission of the human immunodeficiency virus, all phenomena that may be caused by defective cell adhesion. Discoveries made in this area—including those of the IBEC group—will broaden the possibilities for the development of new treatments for these diseases.

These findings and the technology now available also open up the possibility of exploring other areas of cell biology with nanoscale imaging because the organization of proteins in the cell membrane is a general mechanism in the rapid response of a cell to its environment. Specifically, further research could shed light on the processes involved in the adhesion of other integrins, which also involves interaction with lipid rafts.

Reference article: Thomas S. van Zanten, Alessandra Cambi, Marjolein Koopman, Ben Joosten, Carl G. Figdor y María F. García-Parajo (2009). Hotspots of GPI-anchored proteins and inegrin nanoclusters function as nucleation sites for cell adhesion. PNAS