Drosophila neuroligin 2 is required presynaptically and postsynaptically for proper synaptic differentiation and synaptic transmission.

Abstract

Trans-synaptic adhesion between Neurexins (Nrxs) and Neuroligins (Nlgs) is thought to be required for proper synapse organization and modulation, and mutations in several human Nlgs have shown association with autism spectrum disorders. Here we report the generation and phenotypic characterization of Drosophila neuroligin 2 (dnlg2) mutants. Loss of dnlg2 results in reduced bouton numbers, aberrant presynaptic and postsynaptic development at neuromuscular junctions (NMJs), and impaired synaptic transmission. In dnlg2 mutants, the evoked responses are decreased in amplitude, whereas the total active zone (AZ) numbers at the NMJ are comparable to wild type, suggesting a decrease in the release probability. Ultrastructurally, the presynaptic AZ number per bouton area and the postsynaptic density area are both increased in dnlg2 mutants, whereas the subsynaptic reticulum is reduced in volume. We show that both presynaptic and postsynaptic expression of Dnlg2 is required to restore synaptic growth and function in dnlg2 mutants. Postsynaptic expression of Dnlg2 in dnlg2 mutants and wild type leads to reduced bouton growth whereas presynaptic and postsynaptic overexpression in wild-type animals results in synaptic overgrowth. Since Nlgs have been shown to bind to Nrxs, we created double mutants. These mutants are viable and display phenotypes that closely resemble those of dnlg2 and dnrx single mutants. Our results provide compelling evidence that Dnlg2 functions both presynaptically and postsynaptically together with Neurexin to determine the proper number of boutons as well as the number of AZs and size of synaptic densities during the development of NMJs.

• Authors: Yu-Chi Chen, Yong Qi Lin, Swati Banerjee, Koen Venken, Jingjun Li, Afshan Ismat, Kuchuan Chen, Lita Duraine, Hugo J Bellen, Manzoor A Bhat
• Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 32 Issue 45 Pg. 16018-30 (Nov 07 2012) ISSN: 1529-2401 [Electronic] United States
• PMID: 23136438 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cell Adhesion Molecules, Neuronal
• Drosophila Proteins
• Nerve Tissue Proteins
• neuroligin 2

Topics

• Animals
• Animals, Genetically Modified
• Cell Adhesion Molecules, Neuronal (genetics, metabolism)
• Drosophila
• Drosophila Proteins (genetics, metabolism)
• Nerve Tissue Proteins (genetics, metabolism)
• Neuromuscular Junction (genetics, metabolism, ultrastructure)
• Post-Synaptic Density (genetics, metabolism, ultrastructure)
• Presynaptic Terminals (metabolism, ultrastructure)
• Synaptic Transmission (physiology)