page 703, Kelso et al. complete the trilogy of actin papers with a detailed biochemical analysis of the Drosophila Kelch protein. Like the Arp2/3 complex, Kelch is required for proper actin organization in ovarian ring canals. Although the structure of Kelch suggested that it might act as a dimeric actin cross-linking protein, this activity had not yet been demonstrated.
In an impressive series of biochemical experiments, the authors demonstrate that purified Kelch can bundle actin filaments through a conserved actin-binding site, and that phosphorylation of a tyrosine residue near the actin-binding site blocks Kelch from interacting with actin. In vivo, Kelch is phosphorylated by a mechanism involving the Src-family kinase src64. A loss-of-function mutation in src64 and a mutation in Kelch that removes the phosphorylation site produce identical ring canal defects.
The authors propose that ring canal growth is driven by actin polymerization and regulated actin cross-linking, in a mechanism similar to plasma membrane movement at the leading edge of motile cells. In this model, src64 phosphorylation of Kelch would be required to break cross-links, allowing rapid turnover of actin monomers. The similarity of src64 and Kelch mutant phenotypes also suggests that Kelch is the primary target of src64 activity during ring canal development. ▪