J. Perroy et al., The C terminus of the metabotropic glutamate receptor subtypes 2 and 7 specifies the receptor signaling pathways, J BIOL CHEM, 276(49), 2001, pp. 45800-45805
There is accumulating evidence that the specificity of the transduction cas
cades activated by G protein-coupled receptors cannot solely depend on the
nature of the coupled G protein. To identify additional structural determin
ants, we studied two metabotropic glutamate (mGlu) receptors, the mGlu2 and
mGlu7 receptors, that are both coupled to G. proteins but are known to aff
ect different effectors in neurons. Thus, the mGlu2 receptor selectively bl
ocks N- and L-type Ca2+ channels via a protein kinase C-independent pathway
, whereas the mGlu7 receptor selectively blocks P/Q-type Ca2+ channels via
a protein kinase C-dependent pathway, and both effects are pertussis toxin-
sensitive. We examined the role of the C-terminal domain of these receptors
in this coupling. Chimeras were constructed by exchanging the C terminus o
f these receptors and transfected into neurons. Different chimeric receptor
s bearing the C terminus of mGlu7 receptor blocked selectively P/Q-type Ca2
+ channels, whereas chimeras bearing the C terminus of mGlu2 receptor selec
tively blocked N- and L-type Ca2+ channels. These results show that the C t
erminus of mGlu2 and mGlu7 receptors is a key structural determinant that a
llows these receptors to select a specific signaling pathway in neurons.