Two distinct signaling pathways upregulate NMDA receptor responses via two distinct metabotropic glutamate receptor subtypes
Standard
Two distinct signaling pathways upregulate NMDA receptor responses via two distinct metabotropic glutamate receptor subtypes. / Benquet, Pascal; Gee, Christine E; Gerber, Urs.
In: J NEUROSCI, Vol. 22, No. 22, 15.11.2002, p. 9679-86.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Two distinct signaling pathways upregulate NMDA receptor responses via two distinct metabotropic glutamate receptor subtypes
AU - Benquet, Pascal
AU - Gee, Christine E
AU - Gerber, Urs
PY - 2002/11/15
Y1 - 2002/11/15
N2 - Molecular processes regulating the gain of NMDA receptors modulate diverse physiological and pathological responses in the CNS. Group I metabotropic glutamate receptors (mGluRs), which neighbor NMDA receptors and which can be coactivated by synaptically released glutamate, couple to several different second messenger pathways, each of which could target NMDA receptors. In CA3 pyramidal cells we show that the activation of mGluR1 potentiates NMDA current via a G-protein-independent mechanism involving Src kinase activation. In contrast, mGluR5-mediated enhancement of NMDA current requires G-protein activation, triggering a signaling cascade including protein kinase C and Src. These results indicate that one neurotransmitter, glutamate, can activate two distinct and independent signaling systems to target the same effector. These two pathways are likely to contribute significantly to the highly differentiated control of NMDA receptor function.
AB - Molecular processes regulating the gain of NMDA receptors modulate diverse physiological and pathological responses in the CNS. Group I metabotropic glutamate receptors (mGluRs), which neighbor NMDA receptors and which can be coactivated by synaptically released glutamate, couple to several different second messenger pathways, each of which could target NMDA receptors. In CA3 pyramidal cells we show that the activation of mGluR1 potentiates NMDA current via a G-protein-independent mechanism involving Src kinase activation. In contrast, mGluR5-mediated enhancement of NMDA current requires G-protein activation, triggering a signaling cascade including protein kinase C and Src. These results indicate that one neurotransmitter, glutamate, can activate two distinct and independent signaling systems to target the same effector. These two pathways are likely to contribute significantly to the highly differentiated control of NMDA receptor function.
KW - Animals
KW - Enzyme Activation
KW - Enzyme Inhibitors
KW - Excitatory Amino Acid Agonists
KW - Excitatory Amino Acid Antagonists
KW - GTP-Binding Proteins
KW - Guanosine Diphosphate
KW - Hippocampus
KW - In Vitro Techniques
KW - N-Methylaspartate
KW - Patch-Clamp Techniques
KW - Protein Kinase C
KW - Protein-Tyrosine Kinases
KW - Pyramidal Cells
KW - Rats
KW - Rats, Wistar
KW - Receptor, Metabotropic Glutamate 5
KW - Receptors, Metabotropic Glutamate
KW - Receptors, N-Methyl-D-Aspartate
KW - Signal Transduction
KW - Thionucleotides
KW - Up-Regulation
KW - src-Family Kinases
M3 - SCORING: Journal article
C2 - 12427823
VL - 22
SP - 9679
EP - 9686
JO - J NEUROSCI
JF - J NEUROSCI
SN - 0270-6474
IS - 22
ER -