A new actin-binding domain glues autophagy together.

Autophagy breaks down nonessential cellular components to replenish macromolecular building blocks during starvation. Nevertheless, the downstream events regulating vesicle trafficking during this essential cellular process are not yet fully defined. Xu et al. combined approaches of crystallography, biochemistry, and cell biology to show that the guanine nucleotide exchange factor DENND3 contains an actin-binding site they call "PHenn domain" in a region previously thought to be unstructured. PHenn domain binding to microfilaments is necessary for DENND3's participation in autophagy, providing a new link between autophagic stimulation and actin microfilaments. The findings by Xu et al. shed important new light on how membrane trafficking participates in critical steps of autophagy in relationship with actin microfilaments.