Multi-domain scaffolding proteins are important for cell polarity because they target proteins to precise subdomains. Margolis's group has now identified a new multiprotein complex that localizes to tight junctions and is therefore a strong candidate for regulating epithelial cell polarity.

The authors found that Pals1, a membrane-associated guanylate kinase (Maguk) scaffolding protein with several protein-interaction domains, localizes to tight junctions, and then identified one potential protein — Pals1-associated tight junction protein (PATJ) — that might target it there. PATJ binds to a distinct domain (L27N) of Pals1 through a new protein–protein interaction domain that the authors called a Maguk recruitment (MRE) domain.

PATJ was then shown to be part of a ternary complex that binds not only Pals1, but also CRB1, the human homologue of Drosophila melanogaster Crumbs. But PATJ and CRB1 don't bind directly to each other, which indicates that Pals1 probably functions as an adaptor. Similarly, in Drosophila, Crumbs binds the Pals1 orthologue, Stardust, but doesn't bind the PATJ homologue, Discs Lost.

Discs Lost and Crumbs are both essential for cell polarity and have also been implicated in the localization of adherens junctions. So, although the exact function of the Pals1 complex needs further study, its conservation from fly to human indicates the importance of this complex.