Waves of Separation

Abstract

Cell Biology During exocytosis of secretory granules, the actin cortex has two opposing roles: It can act as a mechanical barrier impeding access to the plasma membrane, yet it can also act as a carrier that facilitates secretion. The mechanism by which cells resolve this apparent paradox has been unclear. Working with cultured mast cells, Wollman and Meyer found that cells use phase-shifted oscillations of Ca2÷ and F-actin assembly to create a cyclic secretory engine that enhances the rate of exocytosis of secretory granules. The cellwide cortical actin oscillations were initiated by Ca2÷ and phosphatidylinositol 4,5-bisphosphate oscillations that promoted oscillations of N-WASP recruitment (an actin nucleator), thus triggering waves of cortical F-actin assembly and disassembly. These waves of assembly and disassembly alternately allow secretory granules to bind and then move through the cortex en route to Ca2÷-stimulated fusion with the plasma membrane. By examining secretion from single cells, the oscillations could be observed to increase the secretion rate, as also predicted by a mathematical model. This oscillatory dynamics may thus allow cells to separate the two opposing roles of the actin cortex (barrier and carrier) temporally and thereby increase secretion efficiency. Nat. Cell Biol. 14 , 1261 (2012).