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The synaptic glycoprotein neuroplastin is involved in long-term potentiation at hippocampal CA1 synapses

  1. E. D. Gundelfinger*††
  1. *Leibniz Institute for Neurobiology, Brenneckestrasse 6, 39118 Magdeburg, Germany; †Institute of Pharmacology and Toxicology, ‡Institute of Medical Neurobiology, Otto von Guericke University, Leipziger Strasse 44, 39120 Magdeburg, Germany; ‖School of Biological Sciences, Royal Holloway University of London, Egham, Surrey TW20 OEX, United Kingdom; **Institute of Anatomy, Westfälische Wilhelms University, 48149 Münster, Germany; and ‡‡Facultad de Medicina, Universidad de los Andes, San Carlos de Apoquindo 2200, Santiago, Chile

  1. Edited by James L. McGaugh, University of California, Irvine, CA, and approved February 14, 2000 (received for review September 10, 1999)

Abstract

Neuroplastin-65 and -55 (previously known as gp65 and gp55) are glycoproteins of the Ig superfamily that are enriched in rat forebrain synaptic membrane preparations. Whereas the two-Ig domain isoform neuroplastin-55 is expressed in many tissues, the three-Ig domain isoform neuroplastin-65 is brain-specific and enriched in postsynaptic density (PSD) protein preparations. Here, we have assessed the function of neuroplastin in long-term synaptic plasticity. Immunocytochemical studies with neuroplastin-65-specific antibodies differentially stain distinct synaptic neuropil regions of the rat hippocampus with most prominent immunoreactivity in the CA1 region and the proximal molecular layer of the dentate gyrus. Kainate-induced seizures cause a significant enhancement of neuroplastin-65 association with PSDs. Similarly, long-term potentiation (LTP) of CA1 synapses in hippocampal slices enhanced the association of neuroplastin-65 with a detergent-insoluble PSD-enriched protein fraction. Several antibodies against the neuroplastins, including one specific for neuroplastin-65, inhibited the maintenance of LTP. A similar effect was observed when recombinant fusion protein containing the three extracellular Ig domains of neuroplastin-65 was applied to hippocampal slices before LTP induction. Microsphere binding experiments using neuroplastin-Fc chimeric proteins show that constructs containing Ig1–3 or Ig1 domains, but not Ig2–3 domains mediate homophilic adhesion. These data suggest that neuroplastin plays an essential role in implementing long-term changes in synaptic activity, possibly by means of a homophilic adhesion mechanism.

Footnotes

    • ↵§ K.-H.S., H.M., K.L., and S.S. contributed equally to this work.

    • ↵ Present address: Institute of Human Genetics, Otto von Guericke University, 39120 Magdeburg, Germany.

    • ↵†† To whom reprint requests should be addressed. E-mail: gundelfinger{at}ifn-magdeburg.de.

    • This paper was submitted directly (Track II) to the PNAS office.

    • Article published online before print: Proc. Natl. Acad. Sci. USA, 10.1073/pnas.080389297.

    • Article and publication date are at www.pnas.org/cgi/doi/10.1073/pnas.080389297

  • Abbreviations

    ACSF,
    artificial cerebrospinal fluid;
    CAM,
    cell adhesion molecule;
    NCAM,
    neural CAM;
    fEPSP,
    field excitatory postsynaptic potential;
    np65,
    neuroplastin-65;
    np55,
    neuroplastin-55;
    LTP,
    long-term potentiation;
    PSD,
    postsynaptic density;
    SM,
    synaptic membrane
    • Received September 10, 1999.

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