Functional and phosphoproteomic analysis of β-adrenergic receptor signaling at excitatory synapses in the CA1 region of the ventral hippocampus.

Autor: Jami SA; Molecular, Cellular, and Integrative Physiology Interdepartmental PhD Program, University of California, Los Angeles, Los Angeles, CA, USA., Wilkinson BJ; Zilkha Neurogenetic Institute, Los Angeles, CA, USA., Guglietta R; Interdepartmental PhD Program for Neuroscience, University of California, Los Angeles, Los Angeles, CA, USA., Hartel N; Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, CA, USA., Babiec WE; Undergraduate Interdepartmental Program for Neuroscience, University of California, Los Angeles, Los Angeles, CA, USA., Graham NA; Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, CA, USA., Coba MP; Zilkha Neurogenetic Institute, Los Angeles, CA, USA.; Department of Psychiatry and Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.; Department of Physiology and Neuroscience, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA., O'Dell TJ; Integrative Center for Learning and Memory, Brain Research Institute, University of California, Los Angeles, Los Angeles, CA, USA. todell@mednet.ucla.edu.; Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. todell@mednet.ucla.edu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2023 May 09; Vol. 13 (1), pp. 7493. Date of Electronic Publication: 2023 May 09.
DOI: 10.1038/s41598-023-34401-7
Abstrakt: Activation of β-adrenergic receptors (β-ARs) not only enhances learning and memory but also facilitates the induction of long-term potentiation (LTP), a form of synaptic plasticity involved in memory formation. To identify the mechanisms underlying β-AR-dependent forms of LTP we examined the effects of the β-AR agonist isoproterenol on LTP induction at excitatory synapses onto CA1 pyramidal cells in the ventral hippocampus. LTP induction at these synapses is inhibited by activation of SK-type K + channels, suggesting that β-AR activation might facilitate LTP induction by inhibiting SK channels. However, although the SK channel blocker apamin enhanced LTP induction, it did not fully mimic the effects of isoproterenol. We therefore searched for potential alternative mechanisms using liquid chromatography-tandem mass spectrometry to determine how β-AR activation regulates phosphorylation of postsynaptic density (PSD) proteins. Strikingly, β-AR activation regulated hundreds of phosphorylation sites in PSD proteins that have diverse roles in dendritic spine structure and function. Moreover, within the core scaffold machinery of the PSD, β-AR activation increased phosphorylation at several sites previously shown to be phosphorylated after LTP induction. Together, our results suggest that β-AR activation recruits a diverse set of signaling pathways that likely act in a concerted fashion to regulate LTP induction.
(© 2023. The Author(s).)
Databáze: MEDLINE
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