An NMDA receptor ER retention signal regulated by phosphorylation and alternative splicing.
Formation of mature excitatory synapses requires the assembly and delivery of NMDA receptors to the neuronal plasma membrane. A key step in the trafficking of NMDA receptors to synapses is the exit of newly assembled receptors from the endoplasmic reticulum (ER). Here we report the identification of an RXR-type ER retention/retrieval motif in the C-terminal tail of the NMDA receptor subunit NR1 that regulates receptor surface expression in heterologous cells and in neurons. In addition, we show that PKC phosphorylation and an alternatively spliced consensus type I PDZ-binding domain suppress ER retention. These results demonstrate a novel quality control function for alternatively spliced C-terminal domains of NR1 and implicate both phosphorylation and potential PDZ-mediated interactions in the trafficking of NMDA receptors through early stages of the secretory pathway.
Scott
D B
DB
Program in Cell and Molecular Biology and Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Blanpied
T A
TA
Swanson
G T
GT
Zhang
C
C
Ehlers
M D
MD
D017398:Alternative Splicing; D020816:Amino Acid Motifs / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D021382:Protein Sorting Signals / Q000502:physiology*; D017434:Protein Structure, Tertiary / Q000502:physiology; D021122:Protein Subunits; D051381:Rats; D015375:Receptors, Interleukin-2 / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000235:genetics; D014162:Transfection
C409466:NR1 NMDA receptor; D021382:Protein Sorting Signals; D021122:Protein Subunits; D015375:Receptors, Interleukin-2; D016194:Receptors, N-Methyl-D-Aspartate; D018168:Receptors, Retinoic Acid; D011993:Recombinant Fusion Proteins; D047488:Retinoid X Receptors; D014157:Transcription Factors; D011493:Protein Kinase C