In insects, septate junctions localize to the apico-lateral domain of epithelial cells underneath the zonula adherens and play the role of the vertebrate tight junctions by preventing paracellular diffusion . Septate junctions are also found between the glial cells that isolate the brain and peripheral nerves and are required for blood-nerve barrier formation in Drosophila . The machinery providing axonal insulation has been conserved for a part during evolution since, in vertebrate myelinated axons, septate-like junctions attach the terminal myelin loops to the axonal membrane at paranodes. Both the ultrastructural feature and the molecular composition of Drosophila septate junctions and vertebrate paranodal junctions are highly conserved [3, 4]. Septate junctions are formed by strands of regularly spaced inter-membrane particles. A complex of CAMs including Nrx IV, Cont and Nrg is critically involved in the organization of septate junctions in Drosophila whereas the homologous molecules, Caspr/Paranodin, Contactin and Neurofascin-155 are required for the formation of paranodal junctions in vertebrates .
Nrx IV is a transmembrane molecule with a multimodular ectodomain including several laminin-G and EGF-like domains. Nrx IV interacts in cis with Cont, a glypiated CAM of the Ig superfamily (Ig-CAM), which only displays heterophilic binding activity [6, 7]. Nrg is a homophilic transmembrane Ig-CAM of the L1 family [8, 9] that associates with Cont and Nrx IV at septate junctions. The cytoplasmic tail of Nrx IV contains a binding site for Coracle (Cora), a member of the Four-point-one, Ezrin, Radixin, Moesin (FERM) family . It also includes a C-ter PDZ-binding motif interacting with the membrane associated guanylate kinase (MAGUK) Varicose (Vari) .
In Drosophila, null mutation of each of the nrx IV, cont or nrg genes induces embryonic lethality with breakdown of the trans-epithelial and blood-nerve barriers and alteration of the septate junctions [6, 12, 13]. In epithelial cells of nrx IV null mutant, Nrg is misdistributed to the baso-lateral membrane and Cont is diffusely distributed in the cytoplasm indicating that Nrx IV is required for the proper membrane expression of Cont. Reciprocally in cont null mutant, Nrx IV and Nrg are mislocalized to the baso-lateral membrane. Null mutation for cora or vari coding for scaffolding molecules of septate junctions cause barrier defects and mislocalization of Nrx IV. In addition, the PDZ-containing proteins Discs large (Dlg) and Scribble localized at septate junctions, also control the establishment of epithelial cell polarity . Several other membrane molecules have been identified as critical components of the fly septate junctions, including Gliotactin , Lachesin  and the claudin-related molecules Megatrachea  and Sinuous . The loss of one of the septate junction membrane components induces alteration of the trans-epithelial barrier and mislocalization of the Nrx IV complex at the baso-lateral region although the network of interactions bridging together these molecules is still unknown.
An interesting question is whether the strands of septate junctions display either dynamic characteristics or stable behavior to achieve their role of barrier. Drosophila offers a model system to investigate the membrane mobility of CAMs when recruited into highly ordered multimolecular complexes at septate junctions of epithelial cells and when these complexes are disrupted in different genetic backgrounds. We addressed this question using Fluorescence Recovery After Photobleaching (FRAP) analysis in live embryos.