Compartmentalization of phosphatidylinositol 4,5-bisphosphate metabolism into plasma membrane liquid-ordered/raft domains

Abstract

Significance Lipids of bilayer membranes can segregate laterally into distinct liquid phases of different composition called liquid ordered and liquid disordered, and corresponding in the plasma membrane of living cells to nanodomains called raft and nonraft domains. Using Förster resonance energy transfer and genetically expressible protein probes of lipid domains, we find that several steps of the metabolism of phosphoinositide lipids are concentrated in cholesterol-rich liquid-ordered domains of the plasma membrane. The receptor-mediated breakdown and the restoration of major phosphoinositide pools are faster in the liquid-ordered than in the liquid-disordered domains. Thus, the ordered domains host a key lipid signaling system of the cell.