Secretion from the Golgi compartment requires the coordinated biogenesis and fission of transport vesicles. Regulators of the actin network such as cortactin facilitate the elongation and fission of tubular carriers owing to the force provided by directed actin polymerisation. Furthermore, protein kinase D (PKD)-mediated phosphorylation of membrane components has been shown to alter the lipid environment, thus enhancing fission. Interestingly, PKD also phosphorylates cortactin at S298, which impairs actin polymerisation. However, the regulation of actin network formation at the trans-Golgi network (TGN) is mostly unexplored. In this work, Tim Eiseler and colleagues (Weeber et al., 2019) now investigate in more detail the role of PKD in tuning actin polymerisation during fission of Golgi-derived vesicles. They show that PKD2 interacts with and phosphorylates cortactin at the TGN and that this impairs its interaction with WIP, an inhibitor of the actin nucleator N-WASP, thereby inhibiting actin polymerisation. The authors further demonstrate that activated Cdc42, which acts upstream of N-WASP, inhibits PKD2; this results in a shift to non-S298 phosphorylated cortactin that is able to interact with WIP and sequester it from N-WASP, thus enhancing synergistic actin polymerisation, as well as secretion. Based on their findings, the authors propose a model whereby PKD2 and cortactin help to precisely time actin polymerisation to when the lipid environment of the TGN represents a fission-competent state.
