Lipid-protein cargo transfer: a mode of direct cell-to-cell communication for lipids and their associated proteins

Cells in tissues or in experimental cell colonies respond to stimuli in a co-ordinated manner when they are electrically and chemically coupled by gap junctions. These junctions permit the cell-to-cell passage of small molecules, such as inositol tris phosphate (IP(3)) within the colony and are important in co-ordinating tissue activity. This is the only recognised mechanism of direct chemical signalling that does not involve the release of an extracellular messenger between cells. However, the data in this article demonstrates a new mode of intercellular communication. Two potentially important signalling lipids, PIP(2) and ganglioside G-M1 were shown to move between cells in colonies by tracking (i) fluorescent lipids loaded into the plasma membranes of individual cells in a cell colony using a novel micropipette technique and (ii) movement of fluorescent lipids after localised photobleaching. Furthermore, a large protein molecule, cholera toxin B subunit bound to extracellularly facing ganglioside G-M1 was also shown to transfer between cells. The transfer was inhibited by pre-treatment with poly-L-lysine and polyethylenimine, suggesting a role for tight junctions, perhaps by permitting diffusion of lipids and their protein "cargo" across these cell-to-cell contact points. This is a hitherto unsuspected form of molecular signalling within cell colonies and tissues which may have implications for understanding co-ordinated cell colony behaviour.