Plakin repeats (green) take Shot to adherens junctions (red).

The Drosophila Short stop (Shot/Kakapo) gene encodes several protein isoforms, some of which may link integrins to microtubules. In analyzing the Shot locus, Röper and Brown (page 1305) found something odd: a previously unnoticed exon encoding a series of plakin repeats. The only known function of plakin repeats though is to interact with cytoplasmic intermediate filaments, which flies lack.

Based on a biochemical analysis, the plakin repeats are incorporated into a gigantic isoform of Shot that is the third-largest protein discovered in flies. This isoform includes an actin-binding domain, the plakin repeats, a microtubule-binding domain, and spectrin repeats, and is found in adherens junctions, a localization that seems to be determined by a portion of the plakin domain. Reducing the quantity of the largest Shot isoform in early embryos weakens epithelial intercellular contacts, so it is essential for maintaining epithelial integrity.

The authors propose that the giant Shot isoform helps link the adherens junction to an associated belt of actin filaments and microtubules. This novel intermediate filament-independent activity of plakin repeats may be a conserved function of the domain, or it could be a distinct adaptation in insects, where a lack of intermediate filaments left the plakin domain free to evolve a new function. ▪