Homer-1c/Vesl-1L modulates the cell surface targeting of metabotropic glutamate receptor type 1alpha: evidence for an anchoring function.
Homer-1c/Vesl-1L is a 48-kDa protein that forms part of a family of conserved Homer-related proteins that interact with the C-termini of the metabotropic glutamate receptors mGluR1alpha and mGluR5. In order to examine the function of Homer-1c, HEK-293 cells have been transfected with mGluR1alpha, Homer-1c, and both proteins together. When cells were transfected with both proteins, biotinylation of cell surface molecules revealed a significant increase in the amount of receptor and Homer-1c associated with the cell surface compared with cells transfected with mGluR1alpha alone. This finding was paralleled by a concomitant increase in the production of inositol after treatment of the doubly transfected cells with agonist. Cell surface immunostaining of mGluR1alpha showed that Homer-1c can induce clustering of the receptor in the plasma membrane of HEK-293 cells and suggested that the surface receptor was associated with Homer-1c in the plasma membrane. The presence of Homer-1c reduced the rate of loss from the cell surface of mGluR1alpha from 5 to 1%/min and increased the extent of dendritic trafficking of the receptor in rat primary cultured neurons. Our results suggest that Homer-1c increases the cell surface expression of the metabotropic glutamate receptor type 1alpha by increasing its retention in the plasma membrane.
Ciruela
F
F
Medical Research Council Anatomical Neuropharmacology Unit, Mansfield Road, Oxford, OX1 3TH, United Kingdom.
Soloviev
M M
MM
Chan
W Y
WY
McIlhinney
R A
RA
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D004622:Embryo, Mammalian; D000072233:Homer Scaffolding Proteins; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D007700:Kinetics; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection
D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; D007295:Inositol Phosphates; D009479:Neuropeptides; D018094:Receptors, Metabotropic Glutamate; D011994:Recombinant Proteins; C104077:metabotropic glutamate receptor type 1; D016318:Quisqualic Acid