Phospholipid prunes actin branches

A rare membrane phospholipid helps control actin branching on endosomes, Hong et al. show.

Branched actin filaments promote several steps in the endocytic pathway, such as vesicle fission and the formation of endosomal tubules. This type of actin is very dynamic, a property that’s important for its function. However, researchers are still working out how cells fine-tune its stability. The protein cortactin gathers on branched actin networks, enhancing formation of new branches and stabilizing nascent ones. What controls cortactin’s activity isn’t clear. Hong et al. investigated the role of the phospholipid PI(3,5)P₂, which is present on late endosomes and lysosomes and helps manage vesicle trafficking.

The researchers found that cortactin uses its N-terminal actin-binding region to latch onto PI(3,5)P₂ and that this interaction led to the release of cortactin from actin filaments. When the researchers curbed PI(3,5)P₂ synthesis, cortactin accumulated on late endosomes and actin turnover slowed.

In vitro, cortactin promoted the formation and stabilization of actin branches. However, the addition of PI(3,5)P₂ reduced cortactin’s effects. In cells, live imaging showed that PI(3,5)P₂ promoted turnover of endosomal actin if cortactin was present.

The results suggest that PI(3,5)P₂ reduces the stability of branched actin by bumping cortactin from endosomes.