DOI: 10.1523/jneurosci.23-13-05827.2003. NMDA and β<sub>1</sub>-Adrenergic Receptors Differentially Signal Phosphorylation of Glutamate Receptor Type 1 in Area CA1 of Hippocampus

NMDA and β1-Adrenergic Receptors Differentially Signal Phosphorylation of Glutamate Receptor Type 1 in Area CA1 of Hippocampus

10.1523/jneurosci.23-13-05827.2003

Crossref journal-article

Society for Neuroscience

The Journal of Neuroscience (393)

Abstract

Glutamatergic synaptic transmission is mediated primarily through the AMPA-type glutamate receptor (AMPAR); the regulation of this receptor underlies many forms of synaptic plasticity. In particular, phosphorylation of GluR1, an AMPAR subunit, by PKA at serine 845 (S845) increases peak open channel probability and is permissive for both the synaptic expression of the receptor and NMDA-receptor (NMDAR)-dependent long-term potentiation (LTP). Robust NMDAR activation activates PKA as well as other signaling enzymes; however, we find that maximal NMDAR activation dephosphorylates GluR1 at the PKA site S845. Coincident inhibition of phosphatases blocks NMDAR-induced dephosphorylation of S845, but surprisingly does not promote PKA phosphorylation at this site. However, we find that phosphorylation of S845 is increased by the activation of a Gs-coupled receptor, the β1-adrenergic receptor. Interestingly, this divergent signaling occurs despite a more robust coupling of the NMDAR to cAMP generation. In addition, NMDAR activation plays a dominant role in S845 regulation, because activation of β1AR after NMDAR activation has no detectable effect on S845 phosphorylation. These data (1) demonstrate highly specific coupling between these receptors and this substrate, (2) provide an example of a substrate critical in NMDAR-dependent LTP that is incompletely regulated by the NMDAR, and (3) highlight the importance of identifying the physiological signals that regulate these critical synaptic substrates.

Bibliography

Vanhoose, A. M., & Winder, D. G. (2003). NMDA and Î²1-Adrenergic Receptors Differentially Signal Phosphorylation of Glutamate Receptor Type 1 in Area CA1 of Hippocampus. The Journal of Neuroscience, 23(13), 5827â5834.

Authors 2

Amanda M. Vanhoose (first)
Danny G. Winder (additional)

References 40 Referenced 59

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Dates

Type	When
Created	7 years, 4 months ago (April 13, 2018, 6:30 p.m.)
Deposited	2 years, 6 months ago (Feb. 23, 2023, 11:04 a.m.)
Indexed	2 months, 3 weeks ago (June 4, 2025, 9:57 p.m.)
Issued	22 years, 1 month ago (July 2, 2003)
Published	22 years, 1 month ago (July 2, 2003)
Published Online	22 years, 1 month ago (July 2, 2003)
Published Print	22 years, 1 month ago (July 2, 2003)

Funders 0

None

BibTeX

@article{Vanhoose_2003, title={NMDA and β1-Adrenergic Receptors Differentially Signal Phosphorylation of Glutamate Receptor Type 1 in Area CA1 of Hippocampus}, volume={23}, ISSN={1529-2401}, url={http://dx.doi.org/10.1523/jneurosci.23-13-05827.2003}, DOI={10.1523/jneurosci.23-13-05827.2003}, number={13}, journal={The Journal of Neuroscience}, publisher={Society for Neuroscience}, author={Vanhoose, Amanda M. and Winder, Danny G.}, year={2003}, month=jul, pages={5827–5834} }

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