Domains involved in the specificity of G protein activation in phospholipase C-coupled metabotropic glutamate receptors.
G protein-coupled glutamate receptors (mGluR) have recently been characterized. These receptors have seven putative transmembrane domains, but display no sequence homology with the large family of G protein-coupled receptors. They constitute therefore a new family of receptors. Whereas mGluR1 and mGluR5 activate phospholipase C (PLC), mGluR2, mGluR3, mGluR4 and mGluR6 inhibit adenylyl cyclase (AC) activity. The third putative intracellular loop, which determines the G protein specificity in many G protein-coupled receptors, is highly conserved among mGluRs, and may therefore not be involved in the specific recognition of G proteins in this receptor family. By constructing chimeric receptors between the AC-coupled mGluR3 and the PLC-coupled mGluR1c, we report here that both the C-terminal end of the second intracellular loop and the segment located downstream of the seventh transmembrane domain are necessary for the specific activation of PLC by mGluR1c. These two segments are rich in basic residues and are likely to be amphipathic alpha-helices, two characteristics of the G protein interacting domains of all G protein-coupled receptors. This indicates that whereas no amino acid sequence homology between mGluRs and the other G protein-coupled receptors can be found, their G protein interacting domains have similar structural features.
Pin
J P
JP
Centre CNRS-INSERM de Pharmacologie-Endocrinologie, Montpellier, France.
Joly
C
C
Heinemann
S F
SF
Bockaert
J
J
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D004247:DNA; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D017470:Receptors, Glutamate / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D010738:Type C Phospholipases / Q000378:metabolism*; D014981:Xenopus
D017470:Receptors, Glutamate; D004247:DNA; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins