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Adapter protein 14-3-3 is required for a presynaptic form of LTP in the cerebellum

Abstract

Long-term potentiation (LTP) of granule cell–Purkinje cell synapses in the mouse cerebellum requires phosphorylation by protein kinase A of the active-zone protein RIM1α at Ser413. Here, we show that the adapter protein 14-3-3 readily binds phosphorylated Ser413 in RIM1α, and that presynaptic transfection with a dominant-negative 14-3-3η mutant, or a RIM1α mutant with enhanced 14-3-3 binding, inhibits LTP. Thus, RIM1α phosphorylation triggers presynaptic LTP in part through recruitment of 14-3-3 to phospho-Ser413–RIM1α.

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Figure 1: Phospho-RIM1α interacts with 14-3-3.
Figure 2: R56A and R60A mutations of 14-3-3 decrease, whereas a V415P mutation of RIM1α increases, RIM1α–14-3-3 interaction.
Figure 3: Presynaptic manipulations that interfere with RIM1α–14-3-3 interaction impair LTP in granule cell–Purkinje cell pairs.

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Acknowledgements

We thank C. Howell, J. Mayer and S. Durkin for their help with the 14-3-3–RIM1α interaction studies and A.S. Shaw for providing 14-3-3η constructs. R. Bock provided technical assistance. Supported by an Eastern Virginia Medical School Bridge Grant, the Jeffress Memorial Trust (G.L.) and US Public Health Service MH51106 and the Develbiss Fund (D.J.L.).

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Correspondence to György Lonart.

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Simsek-Duran, F., Linden, D. & Lonart, G. Adapter protein 14-3-3 is required for a presynaptic form of LTP in the cerebellum. Nat Neurosci 7, 1296–1298 (2004). https://doi.org/10.1038/nn1348

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