DrosophilaNeurexin IV stabilizes neuron-glia interactions at the CNS midline by binding to Wrapper

Abstract

Ensheathment of axons by glial membranes is a key feature of complex nervous systems ensuring the separation of single axons or axonal fascicles. Nevertheless, the molecules that mediate the recognition and specific adhesion of glial and axonal membranes are largely unknown. We use the Drosophila midline of the embryonic central nervous system as a model to investigate these neuron glia interactions. During development, the midline glial cells acquire close contact to commissural axons and eventually extend processes into the commissures to wrap individual axon fascicles. Here, we show that this wrapping of axons depends on the interaction of the neuronal transmembrane protein Neurexin IV with the glial Ig-domain protein Wrapper. Although Neurexin IV has been previously described to be an essential component of epithelial septate junctions (SJ), we show that its function in mediating glial wrapping at the CNS midline is independent of SJ formation. Moreover, differential splicing generates two different Neurexin IV isoforms. One mRNA is enriched in septate junction-forming tissues, whereas the other mRNA is expressed by neurons and recruited to the midline by Wrapper. Although both Neurexin IV isoforms are able to bind Wrapper, the neuronal isoform has a higher affinity for Wrapper. We conclude that Neurexin IV can mediate different adhesive cell-cell contacts depending on the isoforms expressed and the context of its interaction partners.

Candidate autism gene screen identifies critical role for cell-adhesion molecule CASPR2 in dendritic arborization and spine development

“…Alternatively, CASPR2 may function by transducing an extracellular signal or by enabling another growth-factor receptor to transduce such a signal. Moreover, in Drosophila the CASPR2 homolog neurexin IV binds not only to contactins similar to its vertebrate counterpart (33) but also to other Ig-domain proteins such as neurofascin, wrapper, and roundabout (40)(41)(42). In addition, contactins bind to receptor phospho-tyrosine phosphatases (43,44), which may mediate dendritic growth signaling via the protein tyrosine kinase fyn (45).…”

Cellular Strategies of Axonal Pathfinding

“…4). In the spinal cord, commissural axons appear to interact with side arms of the floor plate cells (Campbell and Peterson 1993), and in the insect CNS, the midline glia extend processes around bundles of commissural neurons, an interaction that is in part implemented by a specific form of neurexin (Stork et al 2009). …”

The CD59 Family Member Leaky/Coiled Is Required for the Establishment of the Blood–Brain Barrier inDrosophila

“…A core component of the Drosophila septate junction is NeurexinIV whose expression requires differential splicing (Baumgartner et al, 1996;Stork et al, 2009). Correct membrane localization of NeurexinIV is brought about by the GPI-linked protein Contactin.…”

“…Transgenic Drosophila strains were generated using phiC31-based transformation according to standard procedures (Bischof et al, 2007). Tissue culture experiments were performed as described (Stork et al, 2009). Phosphatidylinositol-specific phospholipase C (PI-PLC) experiments were performed as described (Koh et al, 2008).…”