Exocytosis and actin polymerization during cell movement are tied together by Xiaofeng Zuo, Wei Guo (University of Pennsylvania, Philadelphia, PA), and colleagues. They find that Exo70, a component of the exocytosis machine called the exocyst, binds to the Arp2/3 complex, a regulator of actin polymerization that helps push out the front of migrating cells.
It has long been thought that exocytosis is directed to the front of moving cells. The added membrane helps the front of the cell to push outwards, and recycles adhesion proteins from the cell rear.
The link to the actin polymerization machinery started with interaction assays using yeast proteins, and was extended to mammalian proteins. The proteins colocalized at the front of moving cells, and depletion of Exo70 decreased lamellipodial size, cell migration speed, and directional persistence.
Overexpressed Exo70 could induce protrusions, but not if its Arp2/3 interaction domain was deleted. EGF induced greater interaction between Exo70 and Arp2/3, and recruited both to the leading edge.
Future work will clarify whether Exo70 is primarily bringing Arp2/3 to the membrane or kinetically regulating its activity. The study underlines, says Guo, that “cell migration is a really coordinated process.”