Abstract
BackgroundNeurexin is a synaptic cell adhesion protein critical for synapse formation and function. Mutations in neurexin and neurexin-interacting proteins have been implicated in several neurological diseases. Previous studies have described Drosophila neurexin mutant phenotypes in third instar larvae and adults. However, the expression and function of Drosophila neurexin early in synapse development, when neurexin function is thought to be most important, has not been described.Methodology/Principal FindingsWe use a variety of techniques, including immunohistochemistry, electron microscopy, in situ hybridization, and electrophysiology, to characterize neurexin expression and phenotypes in embryonic Drosophila neuromuscular junctions (NMJs). Our results surprisingly suggest that neurexin in embryos is present both pre and postsynaptically. Presynaptic neurexin promotes presynaptic active zone formation and neurotransmitter release, but along with postsynaptic neurexin, also suppresses formation of ectopic glutamate receptor clusters. Interestingly, we find that loss of neurexin only affects receptors containing the subunit GluRIIA.Conclusions/SignificanceOur study extends previous results and provides important detail regarding the role of neurexin in Drosophila glutamate receptor abundance. The possibility that neurexin is present postsynaptically raises new hypotheses regarding neurexin function in synapses, and our results provide new insights into the role of neurexin in synapse development.
Highlights
The synaptic clefts of both mammalian central glutamatergic synapses and Drosophila neuromuscular junctions (NMJs) are approximately 20 nanometers wide and contain extracellular domains of cell adhesion proteins and associated molecules [1,2,3,4]
We found that neurexin immunoreactivity was abundant in embryonic NMJs (Fig. 1)
These data suggest that our antibody is specific for neurexin in embryonic NMJs, that neurexin is abundant in embryonic NMJs, and that nrx[313] is a protein null allele or very strong hypomorph
Summary
The synaptic clefts of both mammalian central glutamatergic synapses and Drosophila NMJs are approximately 20 nanometers wide and contain extracellular domains of cell adhesion proteins and associated molecules [1,2,3,4]. Each gene drives expression of two primary neurexin isoforms via alternative promoters: a full-length (alpha) neurexin, and a short (beta) neurexin that contains a common Cterminus [8,20,21]. Each of these six primary mammalian neurexin transcripts can be alternatively spliced to form potentially thousands of different proteins [22,23]. Neurexin is a synaptic cell adhesion protein critical for synapse formation and function. The expression and function of Drosophila neurexin early in synapse development, when neurexin function is thought to be most important, has not been described
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
