Abstract
The structure and function of presynaptic and postsynaptic components of the synapse are highly coordinated. How such coordination is achieved and the molecules involved in this process have not been clarified. Several lines of evidence suggest that presynaptic functionalities are regulated by retrograde mechanisms from the postsynaptic side. We therefore sought postsynaptic mechanisms responsible for trans-synaptic regulation of presynaptic function at excitatory synapses in rat hippocampal CA1 pyramidal neurons. We show here that the postsynaptic complex of scaffolding protein PSD-95 and neuroligin can modulate the release probability of transmitter vesicles at synapse in a retrograde way, resulting in altered presynaptic short-term plasticity. Presynaptic β-neurexin serves as a likely presynaptic mediator of this effect. Our results indicate that trans-synaptic protein-protein interactions can link postsynaptic and presynaptic function.
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Change history
15 January 2008
In the version of this article initially published, Figure 5e was duplicated in Figure 5o. The authors regret the error,which has been corrected in the HTML and PDF versions of the article.
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Acknowledgements
We thank G.-S. Liu, I. Ehrlich, K. Kobayashi and T. Takahashi for advice, and J.C. Howard for editing. Supported by RIKEN and The Ellison Medical Foundation (Y.H.), a Special Postdoctoral Researchers Fellowship from RIKEN (K.F.), the Howard Hughes Medical Institute (M.S.) and the US National Institutes of Health (R01 NS045014 to P.S.).
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Supplementary Fig. 1
Confirmation of the efficacy of PSD-95 RNAi construct. (PDF 2306 kb)
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Futai, K., Kim, M., Hashikawa, T. et al. Retrograde modulation of presynaptic release probability through signaling mediated by PSD-95–neuroligin. Nat Neurosci 10, 186–195 (2007). https://doi.org/10.1038/nn1837
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DOI: https://doi.org/10.1038/nn1837
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