Fig. 7. Alternative multi-protein assemblies of the Crb and Par6-aPKC complexes at the tight junction. Model indicating essential protein-protein interaction partners of Nok within different tissues. Protein-binding domains that are dispensable for Nok function are white. The C-terminal GUK and SH3 domains and the PDZ domain, which is thought to mediate the interaction with Crb proteins, are generally essential within each epithelial tissue. (A) Each of the Nok interaction domains thought to be required for association with Crb, Par6, Patj or Lin-7 is essential for correct polarity of the neural retina, indicating that a highly conserved assembly of Crb and Par6-aPKC complex proteins is present within this tissue. (B) Within the neural tube, interaction with Patj via the L27(N) domain is essential for epithelial integrity. The apical localization of Par6 is independent of the Nok ECR1 domain, which suggests that Par6 associates with Patj within this tissue (see text for further discussion). (C) Association of Nok with Patj or Lin-7 via the two L27 domains is not essential for maintenance of apical ZO-1 junction belts within myocardial cells and for correct myocardial morphogenesis. Therefore, an alternative multi-protein assembly that requires interaction with Par6 via the ECR1 domain may be present within myocardial cells (see text for further discussion). (D) Within RPE cells, Nok requires the PDZ-domain, which is thought to mediate the interaction with Crb, to confer correct polarity to this tissue. Integrity of the RPE is not dependent on the presence of the Nok ECR1 domain (association with Par6) or the two L27 domains (association with Patj and Lin-7). It remains to be investigated whether alternative binding sites are utilized to tether Par6, Lin-7 or Patj to Crb-Nok or whether these proteins are not essential for the maintenance of the Crb complex within the RPE.