The Synaptic Glycoprotein Neuroplastin Is Involved in Long-Term Potentiation at Hippocampal CA1 Synapses

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 97; no. 8; pp. 4327 - 4332
• Main Authors: K.-H. Smalla, Matthies, H., Langnase, K., Shabir, S., Bockers, T. M., Wyneken, U., Staak, S., Krug, M., Beesley, P. W., Gundelfinger, E. D.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 11-04-2000; National Acad Sciences; The National Academy of Sciences
• Subjects: Aggregation; Animals; Antibodies; Antibodies - immunology; Biological Sciences; Cell lines; Hippocampus; Hippocampus - physiology; Immunoglobulins - immunology; Immunoglobulins - metabolism; Immunoglobulins - physiology; Immunohistochemistry; Long term potentiation; Long-Term Potentiation - physiology; Male; Membrane Glycoproteins - immunology; Membrane Glycoproteins - metabolism; Membrane Glycoproteins - physiology; Nerve Tissue Proteins - immunology; Nerve Tissue Proteins - metabolism; Nerve Tissue Proteins - physiology; Neural cell adhesion molecules; Neurons; neuroplastin; Prosencephalon - metabolism; Protein isoforms; Rats; Rats, Wistar; Recombinant Fusion Proteins - metabolism; Seizures; Synapses; Synapses - physiology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.080389297

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-Fcchimeric 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.