Co-expression of metabotropic glutamate receptor type 1α with Homer-1a/Vesl-1S increases the cell surface expression of the receptor

Homer-1a is a 30 kDa protein that forms part of a family of conserved Homer-related proteins that interact with the C-termini of the metabotropic glutamate receptors mGluR1 alpha and mGluR5a. Analysis of HEK-293 cells by PCR showed that they contained mRNA coding for members of the Homer family with the predominant form being Homer-1b, which is consistent with the immunochemical analysis of these cells. Homer-1a could not be detected by immunochemical analysis. To examine the function of Homer-1a, HEK-293 cells were transfected with cDNA encoding mGluR1 alpha or Homer-1a or co-transfected with both cDNAs. When cells were co-transfected with the cDNAs for both proteins, immunofluorescent staining and biotinylation of cell surface molecules revealed a significant increase in the amount of receptor present at the cell surface in contrast to cells transfected with mGluR1 alpha cDNA alone. This finding was consistent with a concomitant increase in the production of inositol phosphates after treatment of the doubly transfected cells with agonist. Intracellular immunostaining for both proteins revealed that they were co-localized and underwent a redistribution into a large vesicular compartment when they were co-expressed.