期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 287, 期 17, 页码 14201-14214出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M111.293175
关键词
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资金
- Deutsche Forschungsgemeinschaft [SFB 779]
- Pakt fur Forschung und Innovation of the Leibniz Society (Wissensgemeinschaft Gottfried Wilhelm Leibniz (WGL))
- European Union [2007-2013]
- Medical University Vienna, Center for Brain Research
gamma-Aminobutyric acid type A (GABA(A)) receptors are pentameric ligand-gated ion channels that mediate fast inhibition in the central nervous system. Depending on their subunit composition, these receptors exhibit distinct pharmacological properties and differ in their ability to interact with proteins involved in receptor anchoring at synaptic or extra-synaptic sites. Whereas GABA(A) receptors containing alpha 1, alpha 2, or alpha 3 subunits are mainly located synaptically where they interact with the submembranous scaffolding protein gephyrin, receptors containing alpha 5 subunits are predominantly found extra-synaptically and seem to interact with radixin for anchorage. Neuroplastin is a cell adhesion molecule of the immunoglobulin superfamily that is involved in hippocampal synaptic plasticity. Our results reveal that neuroplastin and GABA(A) receptors can be co-purified from rat brain and exhibit a direct physical interaction as demonstrated by co-precipitation and Forster resonance energy transfer (FRET) analysis in a heterologous expression system. The brain-specific isoform neuroplastin-65 co-localizes with GABA(A) receptors as shown in brain sections as well as in neuronal cultures, and such complexes can either contain gephyrin or be devoid of gephyrin. Neuroplastin-65 specifically co-localizes with alpha 1 or alpha 2 but not with alpha 3 subunits at GABAergic synapses. In addition, neuroplastin-65 also co-localizes with GABA(A) receptor alpha 5 subunits at extra-synaptic sites. Down-regulation of neuroplastin-65 by shRNA causes a loss of GABA(A) receptor alpha 2 subunits at GABAergic synapses. These results suggest that neuroplastin-65 can co-localize with a subset of GABA(A) receptor subtypes and might contribute to anchoring and/or confining GABA(A) receptors to particular synaptic or extra-synaptic sites, thus affecting receptor mobility and synaptic strength.
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