Tyrosine phosphatases regulate AMPA receptor trafficking during metabotropic glutamate receptor-mediated long-term depression

Peter R. Moult, Clare M. Gladding, Thomas M. Sanderson, Stephen M. Fitzjohn, Zafar I. Bashir, Elek Molnar, Graham L. Collingridge

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Abstract

Two forms of long-term depression (LTD), triggered by activation of NMDA receptors (NMDARs) and metabotropic glutamate receptors (mGluRs), respectively, can be induced at CA1 synapses in the hippocampus. Compared with NMDAR-LTD, relatively little is known about mGluR-LTD. Here, we show that protein tyrosine phosphatase (PTP) inhibitors, orthovanadate and phenylarsine oxide, selectively block mGluR-LTD induced by application of the group I mGluR agonist (RS)-3,5-dihydroxyphenylglycine (DHPG-LTD), because NMDAR-LTD is unaffected by these inhibitors. Furthermore, DHPG-LTD measured using whole-cell recording is similarly blocked by either bath-applied or patch-loaded PTP inhibitors. These inhibitors also block the changes in paired-pulse facilitation and coefficient of variation that are associated with the expression of DHPG-LTD. DHPG treatment of hippocampal slices was associated with a decrease in the level of tyrosine phosphorylation of GluR2 AMPA receptor (AMPAR) subunits, an effect blocked by orthovanadate. Finally, in dissociated hippocampal neurons, orthovanadate blocked the ability of DHPG to reduce the number of AMPA receptor clusters on the surface of dendrites. Again, the effects of PTP blockade were selective, because NMDA-induced decreases in surface AMPAR clusters was unaffected by orthovanadate. Together, these data suggest that activation of postsynaptic PTP results in tyrosine dephosphorylation of AMPARs and their removal from the synapse.
Original languageEnglish
Pages (from-to)2544-2554
Number of pages11
JournalJournal of Neuroscience
Volume26
Issue number9
DOIs
Publication statusPublished - 1 Jan 2006

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Metabotropic Glutamate Receptors
Protein Tyrosine Phosphatases
Vanadates
AMPA Receptors
Phosphoric Monoester Hydrolases
Tyrosine
N-Methyl-D-Aspartate Receptors
Synapses
Patch-Clamp Techniques
N-Methylaspartate
Dendrites
Baths
Hippocampus
Phosphorylation
Neurons
dihydroxyphenylethylene glycol
3,5-dihydroxyphenylglycine
Therapeutics

Cite this

Moult, P. R., Gladding, C. M., Sanderson, T. M., Fitzjohn, S. M., Bashir, Z. I., Molnar, E., & Collingridge, G. L. (2006). Tyrosine phosphatases regulate AMPA receptor trafficking during metabotropic glutamate receptor-mediated long-term depression. Journal of Neuroscience, 26(9), 2544-2554. https://doi.org/10.1523/JNEUROSCI.4322-05.2006
Moult, Peter R. ; Gladding, Clare M. ; Sanderson, Thomas M. ; Fitzjohn, Stephen M. ; Bashir, Zafar I. ; Molnar, Elek ; Collingridge, Graham L. / Tyrosine phosphatases regulate AMPA receptor trafficking during metabotropic glutamate receptor-mediated long-term depression. In: Journal of Neuroscience. 2006 ; Vol. 26, No. 9. pp. 2544-2554.
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Moult, PR, Gladding, CM, Sanderson, TM, Fitzjohn, SM, Bashir, ZI, Molnar, E & Collingridge, GL 2006, 'Tyrosine phosphatases regulate AMPA receptor trafficking during metabotropic glutamate receptor-mediated long-term depression', Journal of Neuroscience, vol. 26, no. 9, pp. 2544-2554. https://doi.org/10.1523/JNEUROSCI.4322-05.2006

Tyrosine phosphatases regulate AMPA receptor trafficking during metabotropic glutamate receptor-mediated long-term depression. / Moult, Peter R.; Gladding, Clare M.; Sanderson, Thomas M.; Fitzjohn, Stephen M.; Bashir, Zafar I.; Molnar, Elek; Collingridge, Graham L.

In: Journal of Neuroscience, Vol. 26, No. 9, 01.01.2006, p. 2544-2554.

Research output: Contribution to journalArticle

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T1 - Tyrosine phosphatases regulate AMPA receptor trafficking during metabotropic glutamate receptor-mediated long-term depression

AU - Moult, Peter R.

AU - Gladding, Clare M.

AU - Sanderson, Thomas M.

AU - Fitzjohn, Stephen M.

AU - Bashir, Zafar I.

AU - Molnar, Elek

AU - Collingridge, Graham L.

PY - 2006/1/1

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N2 - Two forms of long-term depression (LTD), triggered by activation of NMDA receptors (NMDARs) and metabotropic glutamate receptors (mGluRs), respectively, can be induced at CA1 synapses in the hippocampus. Compared with NMDAR-LTD, relatively little is known about mGluR-LTD. Here, we show that protein tyrosine phosphatase (PTP) inhibitors, orthovanadate and phenylarsine oxide, selectively block mGluR-LTD induced by application of the group I mGluR agonist (RS)-3,5-dihydroxyphenylglycine (DHPG-LTD), because NMDAR-LTD is unaffected by these inhibitors. Furthermore, DHPG-LTD measured using whole-cell recording is similarly blocked by either bath-applied or patch-loaded PTP inhibitors. These inhibitors also block the changes in paired-pulse facilitation and coefficient of variation that are associated with the expression of DHPG-LTD. DHPG treatment of hippocampal slices was associated with a decrease in the level of tyrosine phosphorylation of GluR2 AMPA receptor (AMPAR) subunits, an effect blocked by orthovanadate. Finally, in dissociated hippocampal neurons, orthovanadate blocked the ability of DHPG to reduce the number of AMPA receptor clusters on the surface of dendrites. Again, the effects of PTP blockade were selective, because NMDA-induced decreases in surface AMPAR clusters was unaffected by orthovanadate. Together, these data suggest that activation of postsynaptic PTP results in tyrosine dephosphorylation of AMPARs and their removal from the synapse.

AB - Two forms of long-term depression (LTD), triggered by activation of NMDA receptors (NMDARs) and metabotropic glutamate receptors (mGluRs), respectively, can be induced at CA1 synapses in the hippocampus. Compared with NMDAR-LTD, relatively little is known about mGluR-LTD. Here, we show that protein tyrosine phosphatase (PTP) inhibitors, orthovanadate and phenylarsine oxide, selectively block mGluR-LTD induced by application of the group I mGluR agonist (RS)-3,5-dihydroxyphenylglycine (DHPG-LTD), because NMDAR-LTD is unaffected by these inhibitors. Furthermore, DHPG-LTD measured using whole-cell recording is similarly blocked by either bath-applied or patch-loaded PTP inhibitors. These inhibitors also block the changes in paired-pulse facilitation and coefficient of variation that are associated with the expression of DHPG-LTD. DHPG treatment of hippocampal slices was associated with a decrease in the level of tyrosine phosphorylation of GluR2 AMPA receptor (AMPAR) subunits, an effect blocked by orthovanadate. Finally, in dissociated hippocampal neurons, orthovanadate blocked the ability of DHPG to reduce the number of AMPA receptor clusters on the surface of dendrites. Again, the effects of PTP blockade were selective, because NMDA-induced decreases in surface AMPAR clusters was unaffected by orthovanadate. Together, these data suggest that activation of postsynaptic PTP results in tyrosine dephosphorylation of AMPARs and their removal from the synapse.

U2 - 10.1523/JNEUROSCI.4322-05.2006

DO - 10.1523/JNEUROSCI.4322-05.2006

M3 - Article

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SP - 2544

EP - 2554

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

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ER -