A Laminin G-EGF-Laminin G module in Neurexin IV is essential for the apico-lateral localization of Contactin and organization of septate junctions

• Published in: PloS one Vol. 6; no. 10; p. e25926
• Main Authors: Banerjee, Swati, Paik, Raehum, Mino, Rosa E, Blauth, Kevin, Fisher, Elizabeth S, Madden, Victoria J, Fanning, Alan S, Bhat, Manzoor A
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 14.10.2011; Public Library of Science (PLoS)
• Subjects: Alleles; Amino Acid Sequence; Amino acids; Analysis; Animals; Axons; Biological evolution; Biology; Cell adhesion; Cell adhesion & migration; Cell adhesion molecules; Cell Adhesion Molecules, Neuronal - chemistry; Cell Adhesion Molecules, Neuronal - metabolism; Cell division; Cell Polarity; Clonal deletion; Conservation; Contactin; Contactins - metabolism; Curricula; Cytoskeleton; Drosophila; Drosophila melanogaster - metabolism; Drosophila Proteins - chemistry; Drosophila Proteins - metabolism; Electron density; Epidermal growth factor; Epidermal growth factors; Epithelial Cells - metabolism; Epithelium - metabolism; Epithelium - ultrastructure; Gene expression; Gene mutation; Insects; Laboratories; Laminin; Laminin - chemistry; Localization; Medicine; Membranes - metabolism; Molecular biology; Molecular Sequence Data; Morphogenesis; Mutation; Mutation - genetics; Neurobiology; Neurosciences; Physiology; Protein Binding; Protein interaction; Protein Structure, Tertiary; Protein Transport; Protein-protein interactions; Proteins; Sequence Deletion; Signal transduction; Structure-Activity Relationship; Subcellular Fractions - metabolism; Tight Junctions - metabolism; Tight Junctions - ultrastructure; Trends; Wildlife conservation; North Carolina; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0025926

Septate junctions (SJs) display a unique ultrastructural morphology with ladder-like electron densities that are conserved through evolution. Genetic and molecular analyses have identified a highly conserved core complex of SJ proteins consisting of three cell adhesion molecules Neurexin IV, Contactin, and Neuroglian, which interact with the cytoskeletal FERM domain protein Coracle. How these individual proteins interact to form the septal arrays that create the paracellular barrier is poorly understood. Here, we show that point mutations that map to specific domains of neurexin IV lead to formation of fewer septae and disorganization of SJs. Consistent with these observations, our in vivo domain deletion analyses identified the first Laminin G-EGF-Laminin G module in the extracellular region of Neurexin IV as necessary for the localization of and association with Contactin. Neurexin IV protein that is devoid of its cytoplasmic region is able to create septae, but fails to form a full complement of SJs. These data provide the first in vivo evidence that specific domains in Neurexin IV are required for protein-protein interactions and organization of SJs. Given the molecular conservation of SJ proteins across species, our studies may provide insights into how vertebrate axo-glial SJs are organized in myelinated axons.