Involvement of the proximal C terminus of the AMPA receptor subunit GluR1 in dendritic sorting

Studies on dendritic sorting of transmembrane proteins in hippocampal neuro ns in culture have shown that these cells use similar mechanisms as epithel ial cells to sort transmembrane proteins to the basolateral membrane domain . However, information is still scarce with regard to which amino acidic se quences are required for dendritic sorting in neurons. The glutamate recept or 1 (GluR1) subunit of the AMPA receptor is present on the dendritic compa rtment of hippocampal neurons in culture. To identify the GluR1 sorting sig nal responsible for dendritic targeting, we have expressed the wild-type Gl uR1, a deletion mutant in the C-terminal cytoplasmic tail, and chimeric Glu R1 proteins in hippocampal neurons using a calcium phosphate transfection m ethod. The recombinant full-length GluR1 is polarized to the dendritic doma in. Truncated GluR1 with a deletion of the C-terminal cytoplasmic tail is s till delivered to the somatodendritic domain. However a chimeric protein ma de of the luminal and transmembrane domain of the influenza virus hemagglut inin (HA) fused to the GluR1 C-terminal cytoplasmic tail (HaemR1) is detect ed in the somatodendritic domain. This finding indicates that the GluR1 C-t erminal cytoplasmic tail contains a dendritic sorting signal, which redirec ts the axonal or axonal-dendritic protein HA to the dendritic compartment e xclusively. Deletion analysis of HaemR1 shows that the proximal segment of the GluR1 C-terminal cytoplasmic tail contains a novel dendritic sorting si gnal.