During cell migration, signalling must be regulated independently at several subcellular locations – for instance, focal adhesions are formed at the leading edge and disassembled at the trailing edge. Such localised regulation has been difficult to study, because interventions typically affect the whole cell. On page , Peter Parker and colleagues address this issue, using a drug-dependent recruitment approach to investigate the atypical PKC (aPKC)-dependent migratory pathway at the leading edge. By using two fusion constructs that dimerise in the presence of the rapamycin analogue rapalogue, the authors target the kinase MEK1 to the leading edge of migration, where it colocalises with paxillin (a focal-adhesion component). Localised MEK1 activity induces the activation of the kinase ERK1/2 at the leading edge, which in turn leads to paxillin phosphorylation at focal adhesions. Notably, in cells in which aPKC is inhibited, leading-edge activation of MEK1 partially rescues migration; by contrast, targeting MKK4 (which activates JNK) does not rescue migration. The authors conclude that ERK1/2, but not JNK, is a component of the aPKC-dependent migratory pathway. These results highlight the role of compartment-specific signalling in cell migration.
