Abstract
BackgroundGenetic analysis of the Drosophila septate junctions has greatly contributed to our understanding of the mechanisms controlling the assembly of these adhesion structures, which bear strong similarities with the vertebrate tight junctions and the paranodal septate junctions. These adhesion complexes share conserved molecular components and have a common function: the formation of paracellular barriers restraining the diffusion of solutes through epithelial and glial envelopes.Methodology/Principal FindingsIn this work we characterise the function of the Drosophila cold gene, that codes for a protein belonging to the Ly6 superfamily of extracellular ligands. Analysis of cold mutants shows that this gene is specifically required for the organisation of the septate junctions in epithelial tissues and in the nervous system, where its contribution is essential for the maintenance of the blood-brain barrier. We show that cold acts in a cell autonomous way, and we present evidence indicating that this protein could act as a septate junction component.Conclusion/SignificanceWe discuss the specific roles of cold and three other Drosophila members of the Ly6 superfamily that have been shown to participate in a non-redundant way in the process of septate junction assembly. We propose that vertebrate Ly6 proteins could fulfill analogous roles in tight junctions and/or paranodal septate junctions.
Highlights
The proteins of the Ly6 superfamily are an ancient feature of metazoan genomes, as genes coding for the Ly6 motif have been identified in a wide variety of animal clades, ranging from cnidarians [1] to vertebrates [2,3]
We show that cold mutants display similar phenotypes to those seen in bou alleles [7], indicating that cold is essential for the organisation of the insect septate junctions (SJ)
In this work we show that cold is required for the organisation of the SJ in both epithelial tissues and in glial cells, where its activity is required for maintenance of the blood brain barrier
Summary
The proteins of the Ly6 superfamily are an ancient feature of metazoan genomes, as genes coding for the Ly6 motif have been identified in a wide variety of animal clades, ranging from cnidarians [1] to vertebrates [2,3]. The Ly6 domains are small extracellular modules of about 100 residues characterised by presence of 4–6 pairs of cysteines placed in stereotypical positions [4] These conserved residues form internal disulphide bridges that stabilise the conformation of the motif, but the rest of the protein sequence can vary to a remarkable extent. Despite this variability, these proteins adopt upon folding comparable three-dimensional structures, that are characterised by an internal hydrophobic core supporting three protruding fingers [4]. These adhesion complexes share conserved molecular components and have a common function: the formation of paracellular barriers restraining the diffusion of solutes through epithelial and glial envelopes
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