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Differential control of presynaptic efficacy by postsynaptic N-cadherin and β-catenin

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Abstract

N-cadherin is a homophilic adhesion protein that remains expressed at mature excitatory synapses beyond its developmental role in synapse formation. We investigated the trans-synaptic activity of N-cadherin in regulating synapse function in rodent cultured hippocampal neurons using optical methods and electrophysiology. Interfering with N-cadherin in postsynaptic neurons reduced basal release probability (pr) at inputs to the neuron, and this trans-synaptic impairment of release accompanied impaired vesicle endocytosis. Moreover, loss of the GluA2 AMPA-type glutamate receptor subunit, which decreased pr by itself, occluded the interference with postsynaptic N-cadherin. The loss of postsynaptic N-cadherin activity, however, did not affect the compensatory upregulation of pr induced by chronic activity silencing, whereas postsynaptic β-catenin deletion blocked this presynaptic homeostatic adaptation. Our findings suggest that postsynaptic N-cadherin helps link basal pre- and postsynaptic strengths to control the pr offset, whereas the pr gain adjustment requires a distinct trans-synaptic pathway involving β-catenin.

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Figure 1: Postsynaptic expression of DN-NCad decreases presynaptic proteins.
Figure 2: Ultrastructural analysis of synaptic vesicle distribution.
Figure 3: Disrupting postsynaptic N-cadherin activity decreases the size of the recycling synaptic vesicle pool.
Figure 4: Postsynaptic N-cadherin modulates neurotransmitter release probability.
Figure 5: Presynaptic disruption of N-cadherin activity does not affect neurotransmitter release.
Figure 6: GluA2 is a possible effector of the trans-synaptic regulation of release by N-cadherin.
Figure 7: N-cadherin and β-catenin are differentially required for homeostatic regulation of release probability.
Figure 8: Disrupting postsynaptic N-cadherin activity affects synaptic vesicle endocytosis.

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Acknowledgements

We thank R. Kemler (Max Planck Institute of Immunology) for β-catenin floxed mice, T. Okuda (Keio University) and M. Passafaro (University of Milan) for sharing plasmids, D. Elliott for expert technical assistance and the members of the Goda laboratory for discussions. This work was supported by the UK Medical Research Council, the European Union 7th Framework Program EUROSPIN project and the RIKEN Brain Science Institute.

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Authors and Affiliations

  1. Medical Research Council Laboratory for Molecular Cell Biology and Cell Biology Unit, University College London, London, UK

    Nathalia Vitureira, Mathieu Letellier, Ian J White & Yukiko Goda

  2. RIKEN Brain Science Institute, Wako, Saitama, Japan

    Yukiko Goda

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  1. Nathalia Vitureira
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  2. Mathieu Letellier
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Contributions

N.V. performed all of the experimental work. M.L. contributed electrophysiology experiments and discussion, and I.J.W. performed electron microscopy. N.V. and Y.G. designed the project and wrote the manuscript.

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Correspondence to Yukiko Goda.

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Vitureira, N., Letellier, M., White, I. et al. Differential control of presynaptic efficacy by postsynaptic N-cadherin and β-catenin. Nat Neurosci 15, 81–89 (2012). https://doi.org/10.1038/nn.2995

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