G-protein-independent signaling mediated by metabotropic glutamate receptors.
Synaptically released glutamate activates ionotropic and metabotropic receptors at central synapses. Metabotropic glutamate receptors (mGluRs) are thought to modulate membrane conductances through transduction cascades involving G proteins. Here we show, in CA3 pyramidal cells from rat hippocampus, that synaptic activation of type 1 mGluRs by mossy fiber stimulation evokes an excitatory postsynaptic response independent of G-protein function, while inhibiting an afterhyperpolarization current through a G-protein-coupled mechanism. Experiments using peptide activators and specific inhibitors identified a Src-family protein tyrosine kinase as a component of the G-protein-independent transduction pathway. These results represent the first functional evidence for a dual signaling mechanism associated with a heptahelical receptor such as mGluR1, in which intracellular transduction involves activation of either G proteins or tyrosine kinases.
Heuss
C
C
Brain Research Institute, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
Scanziani
M
M
Gähwiler
B H
BH
Gerber
U
U
D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors / Q000378:metabolism; D000241:Adenosine / Q000494:pharmacology; D000595:Amino Acid Sequence; D027322:Amino Acid Transport System X-AG; D000818:Animals; D002412:Cations / Q000378:metabolism; D004553:Electric Conductivity; D004558:Electric Stimulation; D004789:Enzyme Activation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D058788:GABA-B Receptor Antagonists; D020962:Heterotrimeric GTP-Binding Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000502:physiology; D009924:Organ Culture Techniques; D011188:Potassium / Q000378:metabolism; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018080:Receptors, GABA-B / Q000502:physiology; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D002412:Cations; D018691:Excitatory Amino Acid Antagonists; D058788:GABA-B Receptor Antagonists; D018080:Receptors, GABA-B; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D019061:src-Family Kinases; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; D020962:Heterotrimeric GTP-Binding Proteins; D000241:Adenosine; D011188:Potassium