Coupling profile of the metabotropic glutamate receptor 1alpha is regulated by the C-terminal domain.
The metabotropic glutamate receptor 1alpha (mGluR1alpha) is known to cause various cell responses via coupling with different types of G protein. By using a combination of fluorescent indicators, we simultaneously observed the dual signals of mGluR1alpha, via activation of the Gq and Gs proteins, as increases in the intracellular Ca(2+) and cAMP concentration, respectively. The dual signals are regulated by long C-terminal domain of mGluR1alpha since a short splice variant, mGluR1beta, could not activate the Gs pathway. Cytoskeletal proteins that interact with the long C-terminal tail, such as homer1 and 4.1G, are known to modulate the mGluR1alpha signaling; however, their effects on the dual signaling remain unknown. The simultaneous monitoring demonstrated that the 4.1G behaves as a regulator of dual signaling rather than a simple inhibitor, via its interaction with a cluster of acidic residues in the distal C-tail, which locates close to the important regions for the Gs coupling.
Tateyama
Michihiro
M
Division of Biophysics and Neurobiology, Department of Molecular Physiology, National Institute for Physiological Sciences, Myodaiji, Okazaki, 444-8585, Japan. tateyama@nips.ac.jp
Kubo
Yoshihiro
Y
D020816:Amino Acid Motifs / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002461:Cell Line, Transformed; D006224:Cricetinae; D003412:Cricetulus; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000145:classification / Q000378:metabolism*; D018698:Glutamic Acid / Q000494:pharmacology; D006801:Humans; D016296:Mutagenesis / Q000502:physiology; D017434:Protein Structure, Tertiary; D018094:Receptors, Metabotropic Glutamate / Q000737:chemistry / Q000378:metabolism*; D014162:Transfection / Q000379:methods
D003598:Cytoskeletal Proteins; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D018698:Glutamic Acid; D019204:GTP-Binding Proteins; D002118:Calcium