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A calcineurin/AKAP complex is required for NMDA receptor–dependent long-term depression

Abstract

AKAP79/150 is a protein scaffold that is thought to position specific kinases (protein kinase A and C) and phosphastases (calcineurin) in appropriate synaptic domains so that their activities can regulate excitatory synaptic strength. Using a viral-mediated molecular replacement strategy in rat hippocampal slices, we found that AKAP is required for NMDA receptor–dependent long-term depression solely because of its interaction with calcineurin.

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Figure 1: AKAP knockdown enhances basal AMPAR EPSCs and blocks NMDAR-dependent LTD; effects that are rescued by simultaneous expression of wild-type AKAP-GFP.
Figure 2: PP2B binding to AKAP is required for NMDAR-dependent LTD.

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Acknowledgements

We thank members of the Malenka laboratory for constructive comments on the manuscript and during the course of the experiments. We especially thank D. Goswami for performing the experiments shown in Supplementary Figure 4. This work was supported by a gift from the Morby Charitable Fund for Alzheimer's Research and a grant from the US National Institutes of Health (MH63394). S.J. was supported by a Postdoctoral Fellowship from the Ramon Areces Foundation.

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V.B. generated and tested all of the molecular reagents. S.J. performed the electrophysiology experiments and analyzed the results. S.J. and R.C.M. designed the experiments, interpreted the results and wrote the manuscript.

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Correspondence to Robert C Malenka.

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The authors declare no competing financial interests.

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Supplementary Figures 1–4 and Supplementary Methods (PDF 3090 kb)

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Jurado, S., Biou, V. & Malenka, R. A calcineurin/AKAP complex is required for NMDA receptor–dependent long-term depression. Nat Neurosci 13, 1053–1055 (2010). https://doi.org/10.1038/nn.2613

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