The synaptic glycoprotein neuroplastin is involved in long-term potentiation at hippocampal CA1 synapses.
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-F(c) 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.
Smalla
K H
KH
Leibniz Institute for Neurobiology, Brenneckestrasse 6, 39118 Magdeburg, Germany.
Matthies
H
H
Langnäse
K
K
Shabir
S
S
Böckers
T M
TM
Wyneken
U
U
Staak
S
S
Krug
M
M
Beesley
P W
PW
Gundelfinger
E D
ED
D000818:Animals; D000906:Antibodies / Q000276:immunology; D006624:Hippocampus / Q000502:physiology*; D007136:Immunoglobulins / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D007150:Immunohistochemistry; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D016548:Prosencephalon / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013569:Synapses / Q000502:physiology*
D000906:Antibodies; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; C103658:synaptic glycoprotein gp65