Cell biology: Lipid code for membrane recycling.

Abstract

The sequential action of enzymes has been shown to modify members of a class of membrane lipid called phosphoinositides to direct integral membrane proteins for recycling. See Letter p.408 Directional membrane traffic requires regulated conversion of phosphoinositides (PIs) — membrane phospholipids that act as determinants of membrane identity — by PI metabolizing enzymes. Volker Haucke and co-workers studied the mechanism of PI identity shifts during trafficking from the endosomal system — defined by phosphatidylinositol 3-phosphate (PI(3)P) — to the secretory compartments and the plasma membrane, dominated by phosphatidylinositol 4-phosphate (PI(4)P) and phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2). The authors find that endosomal cargo en route to intracellular destinations can change direction and make its way back to the cell surface by the action of two enzymes. Specifically, PI(3)P on the membrane of these compartments is hydrolysed by the phosphatase MTM1, an enzyme whose loss of function leads to X-linked centronuclear myopathy in humans. This hydrolysis of PI(3)P is accompanied by the generation of PI(4)P through the action of phosphatidylinositol 4-kinase, as well as the recruitment of the exocyst tethering complex to enable subsequent membrane fusion.