Wnt separate ways, met later

In This Issue In This Issue Wnt separate ways, met later embers of the Wnt family of secreted signaling proteins control a wide range of developmental and pathological processes, with each Wnt protein signaling through either the " canonical " or " noncanonical " pathway. Two papers in this issue (and a Comment on page 753) now bring these two pathways together, showing that the noncanonical can directly antagonize the canonical to regulate signals critical for vertebrate body axis determination, limb development, and possibly oncogenesis. The canonical Wnt pathway stabilizes the signaling protein ␤-catenin against degradation, whereas the noncanonical pathway has been considered largely ␤-catenin independent, operating instead through a network of calcium-dependent intermediates. Westfall et al. (page 889) identified the noncanonical Wnt family members in zebrafish and found that a loss of M Linking formins to Arp2/3-actin filaments can be induced to form by either of two pathways, but the elaborate cytoskeletal rearrangements seen in live cells imply that these mechanisms must somehow be coordinated. Now, Carnahan and Gould (page 851) provide the first evidence that a single, highly conserved protein links these two pathways during cytokinesis. Previous work has shown that both the Arp2/3 complex and the formin family of proteins can induce F-actin nucleation, the rate-limiting step in filament formation. The authors show that F in the yeast Schizosacchromyces pombe , the protein Cdc15p interacts directly with both the formin Cdc12p and an Arp2/3 complex regulator. Both Cdc12p and the Arp2/3 complex are essential for forming the cytokinetic actomyosin ring, a structure required for cell cleavage. The Cdc15p–Cdc12p complex appears in a medial structure in cells before ring formation, and Cdc15p is also required for the medial localization of Arp2/3 complex regulators. Cdc15p is highly phosphorylated in inter-phase, but becomes dephosphorylated early in mitosis. The authors propose that dephosphorylation of Cdc15p allows it to associate with Cdc12p and initiate formation of a primary F-actin ring during metaphase. Arp2/3 could then join the complex, driving the maturation of the ring in late anaphase. In interphase, Cdc15p is distributed in a pattern very similar to that of actin patches, raising the possibility that it also coordinates cytoskeletal rearrangements at other times in the cell cycle. As Cdc15p is the founding member of a highly conserved family of proteins, similar mechanisms are likely to be at work in many types of eukaryotic cells. Cdc15p may simply be a scaffold that …