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First published online September 30, 2004
doi: 10.1242/10.1242/dev.01372
1 Neurobiologie des Interactions Cellulaires et Neurophysiopathologie, UMR 6184
CNRS, Institut Jean-Roche, Boulevard Pierre Dramard, 13916 Marseille Cedex 20,
France
2 Department of Cell and Molecular Physiology, Neuroscience Center and
Curriculum in Neurobiology, University of North Carolina School of Medicine,
Chapel Hill, NC 27599-7545, USA
3 Department of Cell and Developmental Biology, University of Michigan, Medical
School, Ann Arbor, MI 48109-0616, USA
Authors for correspondence (e-mail:
sarrailh.c{at}jean-roche.univ-mrs.fr;
manzoor_bhat{at}med.unc.edu)
Accepted 26 July 2004
Septate junctions (SJs) in epithelial and neuronal cells play an important role in the formation and maintenance of charge and size selective barriers. They form the basis for the ensheathment of nerve fibers in Drosophila and for the attachment of myelin loops to axonal surface in vertebrates. The cell-adhesion molecules NRX IV/Caspr/Paranodin (NCP1), contactin and Neurofascin-155 (NF-155) are all present at the vertebrate axo-glial SJs. Mutational analyses have shown that vertebrate NCP1 and its Drosophila homolog, Neurexin IV (NRX IV) are required for the formation of SJs. In this study, we report the genetic, molecular and biochemical characterization of the Drosophila homolog of vertebrate contactin, CONT. Ultrastructural and dye-exclusion analyses of Cont mutant embryos show that CONT is required for organization of SJs and paracellular barrier function. We show that CONT, Neuroglian (NRG) (Drosophila homolog of NF-155) and NRX IV are interdependent for their SJ localization and these proteins form a tripartite complex. Hence, our data provide evidence that the organization of SJs is dependent on the interactions between these highly conserved cell-adhesion molecules.
Key words: Septate Junctions, F3/Contactin, Neurexin IV, Neuroglian, Axo-glial interactions
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