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Subunit dependencies of N-methyl-D-aspartate (NMDA) receptor-induced alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor internalization

Tigaret, C.M.; Thalhammer, A.; Rast, G.F.; Specht, C.G.; Auberson, Y.P.; Stewart, M.G. and Schoepfer, R. (2006). Subunit dependencies of N-methyl-D-aspartate (NMDA) receptor-induced alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor internalization. Molecular Pharmacology, 69(4) pp. 1251–1259.

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N-Methyl-D-aspartate (NMDA) receptor (NMDAR) activity regulates the net number of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (AMPAR) at the cell surface by modulating the balance between AMPAR membrane insertion and endocytosis. In this study, we addressed the role of NMDAR subtypes and of NMDAR-mediated Ca2+ influx in the NMDAR-induced endocytosis of GluR2-containing AMPARs in primary murine hippocampal neurons. We found that NMDAR activation enhanced the endocytosis of AMPARs containing the GluR2 splice variants with short, but not long, cytoplasmic tails. NMDA-induced GluR2 endocytosis was completely inhibited by pharmacological block of NR2B-containing NMDARs. In turn, preferential block of NR2A-containing NMDARs did not affect NMDA-induced AMPAR endocytosis, indicating that AMPAR internalization is controlled by a restricted set of NMDARs. The NMDA-induced GluR2 internalization was also observed in the absence of extracellular Na+ ions, suggesting that membrane depolarization is not a prerequisite for this effect. Furthermore, the activation of Ca2+-impermeable NMDARs containing the mutant NR1(N598R) subunit failed to enhance AMPAR endocytosis, indicating a requirement of Ca2+ influx directly through the NMDAR channels. In summary, our findings suggest that the NMDAR-induced selective internalization of short C-terminal GluR2-containing AMPARs requires a Ca2+ signal that originates from NMDAR channels and is processed in an NMDAR subtype-restricted manner.

Item Type: Journal Article
ISSN: 0026-895X
Extra Information: Some of the symbols may not have transferred correctly into this bibliographic record and/or abstract.
Keywords: N-Methyl-D-aspartate; (NMDA); receptor; NMDAR activity
Academic Unit/Department: Science > Life, Health and Chemical Sciences
Interdisciplinary Research Centre: Biomedical Research Network (BRN)
Item ID: 2290
Depositing User: Michael Stewart
Date Deposited: 29 Jun 2006
Last Modified: 14 Jan 2016 15:47
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