Graziano et al. reveal a new mechanism for controlling actin nucleation.

Proteins that spur actin assembly often work in pairs. In budding yeast, for example, Bud6 teams up with the formin Bni1 to promote actin cable formation. Researchers are unsure if Bud6 also pairs with Bni1’s relative Bnr1. Genetic analyses suggest that Bud6 and Bnr1 combine forces, either directly or indirectly, to induce actin cable growth at the bud neck, but biochemical studies indicate that Bud6 inhibits Bnr1.

Graziano et al. resolved this contradiction, finding that Bnr1 works directly with Bud6 to instigate actin assembly. However, the interaction between the proteins is complicated. The researchers discovered that Bud6 contains a regulatory segment that counteracts its stimulatory effect on Bnr1. Versions of Bud6 containing this region didn’t activate Bnr1 but switched on Bni1 in vitro. However, Bud6 variants lacking the regulatory segment stimulated both formins.

How can Bud6 sometimes stimulate and sometimes inhibit Bnr1? Graziano et al. uncovered a new binding partner of Bud6, which they named Bil1, that latches onto the regulatory region and inactivates it, allowing Bud6 to stimulate Bnr1 and actin cable assembly. Although the researchers haven’t determined how Bil1 cancels the regulatory segment’s inhibition, it might afford the cell more precise control over actin assembly. The study also raises the possibility that other actin-stimulating duos require a similar ignition switch.

et al
J. Cell Biol.

Author notes

Text by Mitch Leslie