Metabotropic glutamate 1alpha and adenosine A1 receptors assemble into functionally interacting complexes.
Recently, evidence has emerged that seven transmembrane G protein-coupled receptors may be present as homo- and heteromers in the plasma membrane. Here we describe a new molecular and functional interaction between two functionally unrelated types of G protein-coupled receptors, namely the metabotropic glutamate type 1alpha (mGlu(1alpha) receptor) and the adenosine A1 receptors in cerebellum, primary cortical neurons, and heterologous transfected cells. Co-immunoprecipitation experiments showed a close and subtype-specific interaction between mGlu(1alpha) and A1 receptors in both rat cerebellar synaptosomes and co-transfected HEK-293 cells. By using transiently transfected HEK-293 cells a synergy between mGlu(1alpha) and A1 receptors in receptor-evoked [Ca(2+)](i) signaling has been shown. In primary cultures of cortical neurons we observed a high degree of co-localization of the two receptors, and excitotoxicity experiments in these cultures also indicate that mGlu(1alpha) and A1 receptors are functionally related. Our results provide a molecular basis for adenosine/glutamate receptors cross-talk and open new perspectives for the development of novel agents to treat neuropsychiatric disorders in which abnormal glutamatergic neurotransmission is involved.
Department of Biochemistry, University of Barcelona, 08028 Barcelona, Spain.
F
F
Ciruela
M
M
Escriche
J
J
Burgueno
E
E
Angulo
V
V
Casado
M M
MM
Soloviev
E I
EI
Canela
J
J
Mallol
W Y
WY
Chan
C
C
Lluis
R A
RA
McIlhinney
R
R
Franco
D000818:Animals; D002460:Cell Line; D002531:Cerebellum / Q000378:metabolism; D006801:Humans; D051381:Rats; D020239:Receptor Cross-Talk; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D015398:Signal Transduction; D013574:Synaptosomes / Q000378:metabolism
D018094:Receptors, Metabotropic Glutamate; D018047:Receptors, Purinergic P1; C104077:metabotropic glutamate receptor type 1