Dysbindin regulates hippocampal LTP by controlling NMDA receptor surface expression

Tina Tze Tsang Tang, Feng Yang, Bo-Shiun Chen, Yuan Lu, Yuanyuan Ji, Katherine W. Roche, Bai Lu

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Abnormalities in NMDA receptor (NMDAR) function have been implicated in schizophrenia. Here, we show that dysbindin, a schizophrenia-susceptibility gene widely expressed in the forebrain, controls the surface expression of NMDARs in a subunitspecific manner. Imaging analyses revealed a marked increase in surface NR2A, but not NR2B, in hippocampal neurons derived from dysbindin-null mutant mice (Dys-/-). Exogenous expression of dysbindin reduced NR2A surface expression in both wild-type and Dys-/- neurons. Biotinylation experiments also revealed an increase in surface expression of endogenous NR2A in Dys-/- neurons. Disruption of the dysbindin gene dramatically increased NR2A-mediated synaptic currents, without affecting AMPA receptor currents, in hippocampal CA1 neurons. The Dys-/- hippocampal slices exhibited an enhanced LTP, whereas basal synaptic transmission, presynaptic properties, and LTD were normal. Thus, dysbindin controls hippocampal LTP by selective regulation of the surface expression of NR2A. These results reveal subunit-specific regulation of NMDARs by dysbindin, providing an unexpected link between these two proteins implicated in schizophrenia.

Original languageEnglish (US)
Pages (from-to)21395-21400
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number50
DOIs
StatePublished - Dec 15 2009

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N-Methyl-D-Aspartate Receptors
Neurons
Schizophrenia
Biotinylation
AMPA Receptors
Prosencephalon
Synaptic Transmission
Genes
Proteins

Keywords

  • Glutamate receptor
  • Schizophrenia
  • Synaptic plasticity

ASJC Scopus subject areas

  • General

Cite this

Dysbindin regulates hippocampal LTP by controlling NMDA receptor surface expression. / Tang, Tina Tze Tsang; Yang, Feng; Chen, Bo-Shiun; Lu, Yuan; Ji, Yuanyuan; Roche, Katherine W.; Lu, Bai.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 50, 15.12.2009, p. 21395-21400.

Research output: Contribution to journalArticle

Tang, Tina Tze Tsang ; Yang, Feng ; Chen, Bo-Shiun ; Lu, Yuan ; Ji, Yuanyuan ; Roche, Katherine W. ; Lu, Bai. / Dysbindin regulates hippocampal LTP by controlling NMDA receptor surface expression. In: Proceedings of the National Academy of Sciences of the United States of America. 2009 ; Vol. 106, No. 50. pp. 21395-21400.
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