Importance of the intracellular domain of NR2 subunits for NMDA receptor function in vivo

Rolf Sprengel, Bettina Suchanek, Carla Amico, Rossella Brusa, Nail Burnashev, Andrei Rozov, OØivind Hvalby, Vidar Jensen, Ole Paulsen, Per Andersen, Jeansok J. Kim, Richard F. Thompson, William Sun, Lorna C. Webster, Seth G.N. Grant, Jens Eilers, Arthur Konnerth, Jianying Li, James O. McNamara, Peter H. Seeburg

Research output: Contribution to journalArticlepeer-review

396 Scopus citations

Abstract

NMDA receptors, a class of glutamate-gated cation channels with high Ca2+ conductance, mediate fast transmission and plasticity of central excitatory synapses. We show here that gene-targeted mice expressing NMDA receptors without the large intracellular C-terminal domain of any one of three NR2 subunits phenotypically resemble mice made deficient in that particular subunit. Mice expressing the NR2B subunit in a C-terminally truncated form (NR2B(ΔC/ΔC) mice) die perinatally. NR2A(ΔC/ΔC) mice are viable but exhibit impaired synaptic plasticity and contextual memory. These and NR2C(ΔC/ΔC) mice display deficits in motor coordination. C-terminal truncation of NR2 subunits does not interfere with the formation of gateable receptor channels that can be synaptically activated. Thus, the phenotypes of our mutants appear to reflect defective intracellular signaling.

Original languageEnglish
Pages (from-to)279-289
Number of pages11
JournalCell
Volume92
Issue number2
DOIs
StatePublished - 23 Jan 1998
Externally publishedYes

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