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

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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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References

  1. Hansel, C., Linden, D.J. & D'Angelo, E. Nat. Neurosci. 4, 467–475 (2001).

    Article  CAS  Google Scholar 

  2. Storm, D.R., Hansel, C., Hacker, B., Parent, A. & Linden, D.J. Neuron 20, 1199–1210 (1998).

    Article  CAS  Google Scholar 

  3. Linden, D.J. & Ahn, S. J. Neurosci. 19, 10221–10227 (1999).

    Article  CAS  Google Scholar 

  4. Castillo, P.E. et al. Nature 415, 327–330 (2002).

    Article  CAS  Google Scholar 

  5. Lonart, G. et al. Cell 115, 49–60 (2003).

    Article  CAS  Google Scholar 

  6. Aitken, A. et al. Biochem. Soc. Trans. 30, 351–360 (2002).

    Article  CAS  Google Scholar 

  7. Berg, D., Holzmann, C. & Reiss O. Nat. Rev. Neurosci. 4, 752–762 (2003).

    Article  CAS  Google Scholar 

  8. Watanabe, M. et al. Brain Res. Mol. Brain Res. 10, 151–158 (1991).

    Article  CAS  Google Scholar 

  9. Thorson, J.A. et al. Mol. Cell. Biol. 18, 5229–5238 (1998).

    Article  CAS  Google Scholar 

  10. Xing, H. et al. EMBO J. 19, 349–358 (2000).

    Article  CAS  Google Scholar 

  11. Sun, L., Bittner, M.A. & Holz, R.W. J. Biol. Chem. 278, 38301–38309 (2003).

    Article  CAS  Google Scholar 

  12. Castillo, P.E. et al. Nature 388, 590–593 (1997).

    Article  CAS  Google Scholar 

  13. Roth, D. & Burgoyne, R.D. FEBS Lett. 374, 77–81 (1995).

    Article  CAS  Google Scholar 

  14. Skoulakis, E.M. & Davis, R.L. Neuron 17, 931–944 (1996).

    Article  CAS  Google Scholar 

  15. Broadie, K., Rushton, E., Skoulakis, E.M. & Davis, R.L. Neuron 19, 391–402 (1997).

    Article  CAS  Google Scholar 

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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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Authors and Affiliations

  1. Department of Pathology & Anatomy, Eastern Virginia Medical School, Norfolk, 23501, Virginia, USA

    Fatma Simsek-Duran & György Lonart

  2. Department of Neuroscience, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, 21205, Maryland, USA

    David J Linden

Authors
  1. Fatma Simsek-Duran
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  2. David J Linden
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  3. György Lonart
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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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