Involvement of the proximal C terminus of the AMPA receptor subunit GluR1 in dendritic sorting.
Studies on dendritic sorting of transmembrane proteins in hippocampal neurons in culture have shown that these cells use similar mechanisms as epithelial cells to sort transmembrane proteins to the basolateral membrane domain. However, information is still scarce with regard to which amino acidic sequences are required for dendritic sorting in neurons. The glutamate receptor 1 (GluR1) subunit of the AMPA receptor is present on the dendritic compartment of hippocampal neurons in culture. To identify the GluR1 sorting signal responsible for dendritic targeting, we have expressed the wild-type GluR1, a deletion mutant in the C-terminal cytoplasmic tail, and chimeric GluR1 proteins in hippocampal neurons using a calcium phosphate transfection method. The recombinant full-length GluR1 is polarized to the dendritic domain. Truncated GluR1 with a deletion of the C-terminal cytoplasmic tail is still delivered to the somatodendritic domain. However a chimeric protein made of the luminal and transmembrane domain of the influenza virus hemagglutinin (HA) fused to the GluR1 C-terminal cytoplasmic tail (HaemR1) is detected in the somatodendritic domain. This finding indicates that the GluR1 C-terminal cytoplasmic tail contains a dendritic sorting signal, which redirects the axonal or axonal-dendritic protein HA to the dendritic compartment exclusively. Deletion analysis of HaemR1 shows that the proximal segment of the GluR1 C-terminal cytoplasmic tail contains a novel dendritic sorting signal.
Ruberti
F
F
Cell Biology and Biophysics Programme, European Molecular Biology Laboratory, 69112 Heidelberg, Germany.
Dotti
C G
CG
D000818:Animals; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D007150:Immunohistochemistry; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D014162:Transfection
D018091:Receptors, AMPA