Importance of the Intracellular Domain of NR2 Subunits for NMDA Receptor Function In Vivo
نویسندگان
چکیده
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(deltaC/deltaC) mice) die perinatally. NR2A(deltaC/deltaC) mice are viable but exhibit impaired synaptic plasticity and contextual memory. These and NR2C(deltaC/deltaC) 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.
منابع مشابه
Calpain-mediated regulation of NMDA receptor structure and function.
Calpains have been previously shown to regulate AMPA receptor properties by producing partial truncation of the C-terminal domains of several receptor subunits. We now report that NMDA receptor subunits, in particular NR2 subunits, are also subjected to calpain-mediated truncation. Treatment of synaptic membranes with calpain I resulted in truncation of both NR1 and NR2 subunits, with the appea...
متن کاملThe effect of morphine dependence on expression of hippocampal N-methyl-D-aspartate receptor subunits in male rats
Introduction: N-methyl-D-aspartate (NMDA) receptors play a pivotal role in the development of tolerance and physical dependence to opiates. Activation of NMDA receptors involves the induction of long term potentiation (LTP) in hippocampus. Our previous study suggested that chronic oral administration of morphine enhanced NMDA dependent LTP in the CA1 area of hippocampal slices of rats. The p...
متن کاملThe N-terminal domains of both NR1 and NR2 subunits determine allosteric Zn2+ inhibition and glycine affinity of N-methyl-D-aspartate receptors.
The N-methyl-D-aspartate (NMDA) subtype of ionotropic glutamate receptors (iGluRs) is a tetrameric protein composed of homologous NR1 and NR2 subunits, which require the binding of glycine and glutamate, respectively, for efficient channel gating. The extracellular N-terminal domains (NTDs) of iGluR subunits show sequence homology to the bacterial periplasmic leucine/isoleucine/valine binding p...
متن کاملPostnatal expression of EAAC1 and glutamate receptor subunits in vestibular nuclear neurons responsive to vertical linear acceleration
Both glutamate receptors and transporters are known to be important in the postsynaptic regulation of glutamate neurotransmission. However, the maturation profile of glutamate transporter EAAC1 and glutamate receptor subunits (NR1, NR2A and NR2B; and GluR 1-4) in functionally activated saccule-related vestibular nuclear neurons of postnatal rats remains unclear. In the present study, conscious ...
متن کاملPostnatal expression of EAAC1 and glutamate receptor subunits in vestibular nuclear neurons responsive to vertical linear acceleration
Both glutamate receptors and transporters are known to be important in the postsynaptic regulation of glutamate neurotransmission. However, the maturation profile of glutamate transporter EAAC1 and glutamate receptor subunits (NR1, NR2A and NR2B; and GluR 1-4) in functionally activated saccule-related vestibular nuclear neurons of postnatal rats remains unclear. In the present study, conscious ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Cell
دوره 92 شماره
صفحات -
تاریخ انتشار 1998