Homer-1c/Vesl-1L modulates the cell surface targeting of metabotropic glutamate receptor type 1 alpha: Evidence for an anchoring function

Homer-1c/Vesl-1L is a 48-kDa protein that forms part of a family of conserv ed Homer-related proteins that interact with the C-termini of the metabotro pic glutamate receptors mGluR1 alpha and mGluR5. In order to examine the fu nction of Homer-1c, HEK-293 cells have been transfected with mGluR1 alpha, Homer-1c, and both proteins together. When cells were transfected with both proteins, biotinylation of cell surface molecules revealed a significant i ncrease in the amount of receptor and Homer-1c associated with the cell sur face compared with cells transfected with mGluR1 alpha alone. This finding was paralleled by a concomitant increase in the production of inositol afte r treatment of the doubly transfected cells with agonist. Cell surface immu nostaining of mGluR1 alpha showed that Homer-1c can induce clustering of th e receptor in the plasma membrane of HEK-293 cells and suggested that the s urface receptor was associated with Homer-1c in the plasma membrane. The pr esence of Homer-1c reduced the rate of loss from the cell surface of mGluR1 alpha from 5 to 1%/min and increased the extent of dendritic trafficking o f the receptor in rat primary cultured neurons. Our results suggest that Ho mer-1c increases the cell surface expression of the metabotropic glutamate receptor type lot by increasing its retention in the plasma membrane.