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Postsynaptic translation affects the efficacy and morphology of neuromuscular junctions

Abstract

Long-term synaptic plasticity may be associated with structural rearrangements within the neuronal circuitry1,2. Although the molecular mechanisms governing such activity-controlled morphological alterations are mostly elusive, polysomal accumulations at the base of developing dendritic spines3 and the activity-induced synthesis of synaptic components suggest that localized translation is involved during synaptic plasticity4,5. Here we show that large aggregates of translational components as well as messenger RNA of the postsynaptic glutamate receptor subunit DGluR-IIA6 are localized within subsynaptic compartments of larval neuromuscular junctions of Drosophila melanogaster. Genetic models of junctional plasticity7 and genetic manipulations using the translation initiation factors eIF4E8 and poly(A)-binding protein9 showed an increased occurrence of subsynaptic translation aggregates. This was associated with a significant increase in the postsynaptic DGluR-IIA protein levels and a reduction in the junctional expression of the cell-adhesion molecule Fasciclin II. In addition, the efficacy of junctional neurotransmission and the size of larval neuromuscular junctions were significantly increased. Our results therefore provide evidence for a postsynaptic translational control of long-term junctional plasticity.

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Figure 1: Subsynaptic translation aggregates and their regulation.
Figure 2: Targets of subsynaptic translation.
Figure 3: Subsynaptic translation affects junctional efficacy.
Figure 4: Subsynaptic translation instructs morphological and functional growth of NMJs.

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Acknowledgements

We are indebted to C. S. Goodman, J. Kidokoro, T. Littleton and R. Rivera-Pomar for their gifts of reagents. We thank E. M. Illgen and M. Langegger for technical assistance, and we are grateful to H. Schwarz for his support and advice during ultrastructural studies. We would like to thank W. Hoch and J. Knoblich for comments on the manuscript and helpful discussions. P.E.D.L. and P.L. are grateful to the MRC of Canada for financial support.

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Correspondence to Christoph M. Schuster.

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Sigrist, S., Thiel, P., Reiff, D. et al. Postsynaptic translation affects the efficacy and morphology of neuromuscular junctions. Nature 405, 1062–1065 (2000). https://doi.org/10.1038/35016598

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