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PMID:24554721

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Citation

Herrera-Molina, R, Sarto-Jackson, I, Montenegro-Venegas, C, Heine, M, Smalla, KH, Seidenbecher, CI, Beesley, PW, Gundelfinger, ED and Montag, D (2014) Structure of excitatory synapses and GABAA receptor localization at inhibitory synapses are regulated by neuroplastin-65. J. Biol. Chem. 289:8973-88

Abstract

Formation, maintenance, and activity of excitatory and inhibitory synapses are essential for neuronal network function. Cell adhesion molecules (CAMs) are crucially involved in these processes. The CAM neuroplastin-65 (Np65) highly expressed during periods of synapse formation and stabilization is present at the pre- and postsynaptic membranes. Np65 can translocate into synapses in response to electrical stimulation and it interacts with subtypes of GABAA receptors in inhibitory synapses. Here, we report that in the murine hippocampus and in hippocampal primary culture, neurons of the CA1 region and the dentate gyrus (DG) express high Np65 levels, whereas expression in CA3 neurons is lower. In neuroplastin-deficient (Np(-/-)) mice the number of excitatory synapses in CA1 and DG, but not CA3 regions is reduced. Notably this picture is mirrored in mature Np(-/-) hippocampal cultures or in mature CA1 and DG wild-type (Np(+/+)) neurons treated with a function-blocking recombinant Np65-Fc extracellular fragment. Although the number of GABAergic synapses was unchanged in Np(-/-) neurons or in mature Np65-Fc-treated Np(+/+) neurons, the ratio of excitatory to inhibitory synapses was significantly lower in Np(-/-) cultures. Furthermore, GABAA receptor composition was altered at inhibitory synapses in Np(-/-) neurons as the α1 to α2 GABAA receptor subunit ratio was increased. Changes of excitatory and inhibitory synaptic function in Np(-/-) neurons were confirmed evaluating the presynaptic release function and using patch clamp recording. These data demonstrate that Np65 is an important regulator of the number and function of synapses in the hippocampus.

Links

PubMed PMC3979398 Online version:10.1074/jbc.M113.514992

Keywords

Animals; CA1 Region, Hippocampal/cytology; Cell Count; Dentate Gyrus/cytology; Excitatory Postsynaptic Potentials; Gene Expression Regulation; Glutamic Acid/metabolism; Inhibitory Postsynaptic Potentials; Membrane Glycoproteins/deficiency; Membrane Glycoproteins/metabolism; Mice; Neurons/cytology; Neurons/metabolism; Protein Subunits/metabolism; Protein Transport; Rats; Receptors, GABA-A/metabolism; Synapses/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:BSN

located_in

GO:0098793: presynapse

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:MTAP2

located_in

GO:0030425: dendrite

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:GBRA2

located_in

GO:0098794: postsynapse

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:GBRA2

located_in

GO:0060077: inhibitory synapse

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:GBRA2

located_in

GO:0030425: dendrite

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:GBRA2

located_in

GO:0043025: neuronal cell body

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:NPTN

acts_upstream_of_or_within

GO:0050808: synapse organization

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:5621191

P

  • occurs_in:(EMAPA:35196)|occurs_in:(EMAPA:36480)

Seeded From UniProt

complete

MOUSE:NPTN

acts_upstream_of_or_within

GO:0050804: modulation of chemical synaptic transmission

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:5621191

P

Seeded From UniProt

complete

MOUSE:NPTN

acts_upstream_of_or_within

GO:1904861: excitatory synapse assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:5621191

P

Seeded From UniProt

complete

MOUSE:NPTN

acts_upstream_of_or_within

GO:1902683: regulation of receptor localization to synapse

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:5621191

P

Seeded From UniProt

complete

MOUSE:GEPH

located_in

GO:0098794: postsynapse

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:GEPH

located_in

GO:0030425: dendrite

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:GEPH

located_in

GO:0043025: neuronal cell body

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:HOME1

located_in

GO:0098794: postsynapse

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:BSN

part_of

GO:0098793: presynapse

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:HOME1

part_of

GO:0098794: postsynapse

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

Notes

See also

References

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