Lipid rafts are dynamic assemblies of cholesterol and sphingolipids, which form microenvironments in the lipid bilayer. Raft clustering is proposed to mediate the activation of signalling cascades, perhaps by bringing together different components of the pathway. But what triggers clustering? Reporting in Science, Khan and colleagues now show that, during activation of T cells, a factor that mediates the formation of the immunological synapse is the same protein as that which mediates formation of neuromuscular junctions — agrin.

Khan and colleagues find that, upon activation of primary immune cells, agrin becomes colocalized with the T-cell receptor (TCR) on the cell surface. As neural agrin can induce aggregation of acetylcholine receptors (AChR) on muscle cells, the authors wondered whether expression of agrin in activated lymphocytes can induce aggregation of TCRs. Treating cells with agrin purified from activated cells (agrinact), they showed, triggered lipid raft clustering. Furthermore, agrinact decreases proliferation thresholds — a measure of lymphocyte activation — indicating that clustering modulates signalling.

So it seems that agrin uses a common mechanism in immune cells and neurons — it clusters rafts to concentrate signalling factors. The question now is how agrin causes lipid rafts to cluster.