Many cognitive functions including emotion, attention, language, social behavior, learning and memory depend on proper synaptic connectivity in the brain. Synapses are specialized asymmetric cellular junctions responsible for communication between neurons. Synaptic adhesion molecules, neuroligins and their binding partners, neurexins, have been suggested to play an important role in bridging the pre- and post-synaptic machineries across the synaptic cleft. However, detailed molecular mechanisms of how neuroligins function at the synapse in vivo still remain unclear. Recently, neuroligins and neurexins have drawn increasing attention due to the link between mutations in human NEUROLIGINS and familial autism spectrum disorders (ASDs) (Jamain et al., 2003). Therefore, understanding the role of neuroligins at the synapse may not only improve our knowledge of how synapses are organized but provide insights into the molecular basis of the pathology and etiology of ASDs.
Here we report the generation and phenotypic characterization of Drosophila neuroligin 2 (dnlg2) mutants. Loss of Dnlg2 results in reduced synaptic development at neuromuscular junctions (NMJs) and decreased neurotransmission. dnlg2 mutant synapses display defects in postsynaptic ultrasctural differentiation. Using UAS/Gal4 system, we demonstrat that both presynaptic and postsynaptic Dnlg2 are required for proper bouton growth and synaptic transmission. We also show that postsynaptic overexpression of Dnlg2 leads to reduced bouton number and that both pre- and post-synaptic Dnlg2 overexpression leads to synaptic overgrowth at NMJs. Furthermore, we show that dnlg2 and dnrx double mutants display phenotypes that resemble dnlg2 and dnrx single mutants. Our results are in disagreement at multiple levels with those of Sun et al. (2011) which reported increased neurotransmission in dnlg2 mutants and rescue of synaptic defects by postsynaptic expression of Dnlg2. Our results demonstrate that Dnlg2 functions both pre- and postsynaptically to coordinate synapse development and function at NMJs, thereby raising an interesting possibility that vertebrate Neuroligins may also be required pre- and postsynaptically for proper synapse development and function.
|Advisor:||Bhat, Manzoor A., Crews, Stephen T.|
|Commitee:||Anton, Eva S., Brenman, Jay E., Philpot, Benjamin D.|
|School:||The University of North Carolina at Chapel Hill|
|Department:||Genetics & Molecular Biology|
|School Location:||United States -- North Carolina|
|Source:||DAI-B 74/09(E), Dissertation Abstracts International|
|Subjects:||Molecular biology, Neurosciences, Developmental biology|
|Keywords:||Neural development, Neurexins, Neuroligins, Neurotransmission, Synapses, Synaptic transmission|
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