The relationship between a key phagocytic enzyme and its target is deeper than physical compatibility, Fairn et al. show. Electrical attraction also brings the two molecules together.
During phagocytosis, actin filaments polymerize to extend the cell's pseudopods and then depolymerize when the target has been surrounded. A key controller of these changes is the membrane phospholipid PI4,5P2. It builds up at growing pseudopods and spurs actin to lengthen. Later, it disappears from the base of the forming phagosome, an essential step for the completion of phagocytosis. The kinase PIP5K manufactures PI4,5P2 from another lipid known as PI4P. Fairn et al. tackled the question of how cells manage PIP5K's location and activity.
Because the enzyme's structure isn't known, Fairn et al. modeled its morphology on a similar protein. Their results indicated that one face of PIP5K bristles with positive charges. The inner portion of the plasma membrane, where much of a cell's PI4P resides, is negatively charged, suggesting that electrical attraction, not just structural specificity, draws PIP5K to its substrate.
Supporting the idea, PIP5K molecules let go when the cells’ inner membrane charge was diminished. Mutant PIP5K molecules carrying less positive charge also avoided the membrane.
The researchers conclude that an electrostatic switch controls PIP5K's location. Their scenario suggests that the enzyme trails PI4P to the membrane and makes PI4,5P2 to trigger pseudopod extension. However, another enzyme called PLC-γ begins destroying the negatively charged PI4,5P2, weakening the attraction between the membrane and PIP5K. The enzyme drops off, decreasing PI4,5P2 synthesis. With less of the phosopholipid at the membrane, actin fibers collapse and phagocytosis can wrap up.