Activation of NMDA receptors induces dephosphorylation of DARPP-32 in rat striatal slices
Abstract
In the caudate-putamen the glutamatergic cortical input and the dopaminergic nigrostriatal input have opposite effects on the firing rate of striatal neurons. Although little is known of the biochemical mechanisms underlying this antagonism, one action of dopamine is to stimulate the cyclic AMP-dependent phosphorylation of DARPP-32 (dopamine and cAMP-regulated phospho-protein, of relative molecular mass 32,000 (32K]. This phosphorylation converts DARPP-32 from an inactive molecule into a potent inhibitor of protein phosphatase-1. Here we show that activation of the NMDA (N-methyl-D-aspartate) subclass of glutamate receptors reverses the cAMP-stimulated phosphorylation of DARPP-32 in striatal slices through NMDA-induced dephosphorylation of DARPP-32. Thus, the antagonistic effects of dopamine and glutamate on the excitability of striatal neurons are reflected in antagonistic effects of these neurotransmitters on the state of phosphorylation of DARPP-32. Our results indicate that stimulation of NMDA receptors leads to the activation of a neuronal protein phosphatase, presumably the calcium-dependent phosphatase calcineurin, and show, in an intact cell preparation, that signal transduction in the nervous system can be mediated by protein dephosphorylation.
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“One consequence of the activation of NMDA receptors is stimulation of the calcium- and calmodulin-dependent protein phosphatase calcineurin (Halpain et al., 1990; Quinlan and Halpain, 1996).”
BackgroundSelf-citationThe absence of a major Ca <sup>2+</sup> signaling pathway in GABAergic neurons of the hippocampus
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- Authors
- Halpain, S., Girault, J.-A., & Greengard, P.
- Affiliations
- Rockefeller University (US)
- Inserm (FR)
- Venue
- Nature
- Published
- 1990-01
- Volume
- 343
- Issue
- 6256
- Pages
- 369-372
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2049668076
- Cited by
- 357
- References
- 1
- Citations by year
- 2023: 2 · 2022: 3 · 2020: 3 · 2019: 1 · 2018: 3 · 2017: 4 · 2016: 8 · 2015: 6 · 2014: 10 · 2013: 4 · 2012: 6
- FWCI
- 11.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- NMDA receptor, DARPP-32, dephosphorylation, striatum, protein phosphatase 1, calcineurin, dopamine, glutamate, cAMP signaling, signal transduction, calcium-dependent phosphatase
- MeSH terms
- Cyclic AMP, Animals, Aspartic Acid, Calmodulin-Binding Proteins, Corpus Striatum, Dibenzocycloheptenes, Enzyme Activation, Colforsin, Nerve Tissue Proteins, Phosphates, Phosphoprotein Phosphatases, Phosphoproteins, Phosphorylation, Phosphothreonine, Protein Kinases, Valine, Receptors, N-Methyl-D-Aspartate, N-Methylaspartate, Dizocilpine Maleate, Receptors, Neurotransmitter, Calcineurin, Rats, Dopamine and cAMP-Regulated Phosphoprotein 32, Protein Phosphatase 1
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