The Interactive Fly

Evolutionarily conserved developmental pathways

Septate junctions and MAGUK proteins: Cell-cell interaction and signaling to the interior of cells

The septate junction of Drosophila (see Discs large), present in lieu of the vertebrate tight junction, now rightly deserves closer scrutiny by developmental biologists. Tight junctions in vertebrates are physically more closely associated with the adherens junction, but in Drosophila, septate junctions assume a more basolateral position. Five proteins are now known to be associated with septate junctions: Fasciclin III, Neuroglian, Discs large, Coracle and Expanded. Both Expanded and Coracle are members of the 4.1 family of proteins that includes mammalian ezrin, radixin and moesin. The 4.1 family proteins physically bind cytoskeletal elements.

Mutation of DLG disrupts this association, suggesting a central role for DLG in septate junction structure. DLG mutants show an enhanced level of disc cell proliferation, suggesting a role for the septate junction in regulation of cell growth. Discs large (DLG) is the prototypic member of a growing family of proteins collectively termed membrane-associated guanylate kinase homologs (MAGUKs). Two other Drosophila MAGUK proteins are Dishevelled (involved in segment polarity) and Canoe (involved in Notch and Ras signaling).

All MAGUKs contain a series of domains: either one or three copies of an 80-90 amino acid motif called DHR/PDZ (DLG Homologous Region/PSD-95), DLG, ZO-1, and a region with high similarity to guanylate kinases (GUK). Both the DHR/PDZ and the SH3 domains may serve as sites for protein-protein interactions. The subfamily of MAGUKs (DLG-R) includes DLG, as well as mammalian tight-junction proteins ZO-1 and ZO-2 (Drosophila homolog: Polychaetoid). In DLG-R family members there are three DHR/PDZ domains, each with a three-amino acid deficiency in the ATP binding site within the GUK, making unlikely the existence of guanylate kinase catalytic activity.

The recent finding that a vertebrate DLG homolog, ZO-1, undergoes nuclear localization at the site of wounding, suggests a role for MAGUK proteins in nuclear signaling.

date revised: 15 Nov 96

Developmental Pathways conserved in Evolution

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