A new SUN role – no KASH required?

In eukaryotic cells, a close physical association between the microtubule-organising centre (MTOC) and the nucleus is essential, and its disruption leads to severe cellular abnormalities. MTOC–nucleus attachment is maintained by SUN and KASH proteins, which are found in the inner and outer nuclear membranes, respectively, and typically interact to form nuclear-envelope-spanning LINC complexes. On page 2763, Kathleen Beckingham and colleagues characterise Spag4, one of two Drosophila SUN proteins, with surprising results. The authors first show that Spag4 is testis specific and that spag4 mutant males are sterile. Similar to other SUN proteins, Spag4 is important for MTOC–nucleus attachment; in its absence, the nucleus dissociates from the single spermatid MTOC [the centriole or basal body (BB)] after meiosis in spermatogenesis. Unusually, however, Spag4-mediated centriole–nucleus attachment does not require either of the two Drosophila KASH proteins – instead, it requires the cytoplasmic coiledcoil protein Yuri Gagarin, which was previously shown by the authors’ research group to have a role in BB–nucleus attachment. The authors go on to show that dynein–dynactin is also important in the same pathway, and conclude that Spag4 is an atypical SUN protein that lacks a KASH partner during spermatogenesis. Special delivery to the leading edge 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 2725, 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.