CARBOXYL DOMAIN OF GLUTAMATE RECEPTOR DIRECTS ITS COUPLING TO METABOLIC PATHWAYS

OF the six metabotropic glutamate receptors (mGluRs) only mGluR1 and m GluR5, which possess a large carboxyl terminal domain, are positively linked to phosphoinositide (PI) hydrolysis. We expressed a 3' deletion of mGluR1alpha (mGluR1T) lacking the terminal 290 codons and the full length mGluR1alpha cDNAs in human embryonic kidney 293 cells. Agonist stimulation of both mGluR1alpha and mGluR1T stimulated PI hydrolysis. Glutamate activation of PI hydrolysis was reduced by pertussis toxin when mediated via mGluR1alpha, while mGluR1T required the presence of extracellular Ca2+. Glutamate-mediated reduction of adenylyl cyclase s timulation by forskolin occurred only in mGluR1T-expressing cells. The results suggest that the carboxyl terminal extension directs the coup ling of mGluR1 with different signal transduction pathways.