IKKepsilon: a kinase at the intersection of signaling and membrane traffic

The ability to coordinate membrane trafficking events in space and time is of fundamental importance in biology. Polarized trafficking is essential for processes as diverse as cytokinesis, regulated endocytosis, cell motility, and morphogenesis, yet the interface between cellular signaling systems and the trafficking machinery remains ill defined. Using Drosophila mechanosensory bristle growth as a paradigm for polarized trafficking, a study has uncovered a role for localized activation of the inhibitor of nuclear factor κB kinase, subtype ε (IKKε) at the tip of these bristles, where it regulates the trafficking of recycling endosomal vesicles into and out of the bristle tip. IKKε phosphorylates the Rab11 effector Nuf (which is encoded by nuclear fallout), and in doing so coordinates the interaction between Nuf and the motor protein dynein, which regulates the directionality of membrane traffic by a "motor-switching" mechanism. Similar results in mammalian systems suggest that IKKε-dependent phosphorylation of Rab11 effectors is an evolutionarily conserved mechanism by which cells may regulate polarized growth, and studies of vesicle trafficking in cytokinesis support the concept of motor switching as a generic mechanism to modulate the distribution of endosomes. Phosphorylation of other Rab11 effectors also modulates polarized trafficking in other experimental systems, which hints that similar mechanisms may be widely used to control the directionality of membrane traffic.