Membrane protein sequestering by ionic protein–lipid interactions

Exocytosis in neuronal cells requires the SNARE protein syntaxin-1A, which is clustered at sites where synaptic vesicles are poised to undergo exocytosis. Reinhard Jahn and colleagues use super-resolution stimulated-emission depletion (STED) microscopy to show that syntaxin clusters in the membrane through electrostatic interactions with the strongly anionic lipid phosphatidylinositol-4,5-bisphosphate (PIP2) into 70-nanometre microdomains. The results demonstrate that electrostatic protein–lipid interactions can result in the formation of microdomains independent of cholesterol or lipid phases and have important implications for the organization of the plasma membrane.