The GTPase dynamin is crucial for vesicle fission during endocytosis and secretion, although the precise mechanism by which it exerts this action is unclear. But can dynamin also influence actin dynamics? Such a relationship was first proposed on the basis that disrupting dynamin function in vitro leads to defects in growth cone motility, and was further substantiated by reports showing that dynamin interacts with actin-regulatory proteins and localizes at actin-rich sites. Two reports in the Proceedings of the National Academy of Sciences now provide evidence that dynamin can control actin nucleation from membranes, thereby regulating comet formation and movement.

To explore a functional link between dynamin and actin, the groups — one led by De Camilli and the other by McNiven — studied the regulation of actin nucleation in actin comets. Actin comets are induced by infection with Listeria monocytogenes or by the accumulation of phosphatidylinositol 4,5-bisphosphate (through the overexpression of phosphatidylinositol phosphate 5-kinase), which induces the activity of actin-regulatory proteins. By tagging dynamin 2 with green fluorescent protein (GFP) and staining for filamentous (F-)actin using phalloidin or the actin-binding protein cortactin, both groups showed that the pattern of GFP fluorescence strongly resembled that of F-actin in the comets. Dynamin was further enriched at the tips of vesicles near the membrane.

Live imaging confirmed that dynamin is incorporated into the forming comets. But does it have an active function in these structures? To test this, both groups made use of dynamin mutants to assess any changes in actin tail formation or dynamics. GTPase-deficient dynamin–GFP mutants — which exert a dominant-negative effect on endocytosis — reduced the number and the speed of comets, and caused them to appear short and curled.

The region of dynamin that directly binds to cortactin, in addition to other actin-regulatory proteins, is its proline-rich domain (PRD), so its involvement in targeting dynamin to actin comets was studied using a PRD-deletion mutant (dynaminΔPRD–GFP). Cells expressing dynaminΔPRD–GFP also formed fewer comets but, unlike the GTPase-deficient mutant, the comets were longer. Significantly, dynaminΔPRD–GFP couldn't be detected in the comets, indicating that the PRD is required to target dynamin to these — and possibly other — actin structures.

So, what is the functional role of dynamin in actin comets? Given its ability to bind to components of the actin-nucleating machinery, we could speculate that dynamin regulates actin-nucleation. In addition, on the basis that it can also associate with the lipid bilayer, its role could be to direct this nucleation to specific sites, such as the coated pits involved in endocytosis. It is also likely, however, that the interaction between dynamin and actin occurs at non-endocytic sites.