# Role of PSD-95-linked PDE4A5 in Regulation of AMPA Receptors

> **NIH NIH F99** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2024 · $42,826

## Abstract

PROJECT SUMMARY
Signaling by cAMP plays a critical role in synaptic plasticity and memory. The b2-adrenergic receptor (β2AR)
forms a unique signaling complex with AMPARs that also includes Gs, adenylyl cyclase (AC), and the cAMP-
dependent kinase. Norepinephrine (NE) stimulates via β2AR -cAMP - PKA the phosphorylation of the AMPAR
GluA1 subunit on S845, promoting AMPAR trafficking to the postsynaptic membrane. A primary mechanism of
long-term potentiation (LTP) of synaptic transmission, which underlies learning and memory, is the accumulation
of AMPAR at the postsynaptic site. Members of the Phosphodiesterase 4 family (PDE4A-D) curb cAMP signaling
by hydrolyzing cAMP. Sleep deprivation stimulates expression of the PDE4A isomer PDE4A5, which impairs
hippocampal long-term potentiation (LTP) and knock down of PDE4A5 rescues learning deficits. Therefore,
pharmacological targeting of PDE4A5 may alleviate cognitive deficits in brain disorders. In Aim 1, we found that
PDE4A5 binds with its unique ~100 amino acid long N-terminus (NT) to the SH3 domain of PSD-95. PSD-95
anchors AMPARs. For the remainder of my PhD. I propose to define the functional role of PDE4A5 and its
association with PSD-95 in AMPAR receptor trafficking. For Aim 2, my postdoctoral position in another lab, I
consider expanding this project by employing advanced imaging methods for cAMP signaling and super
resolution analysis of AMPAR localization in postsynaptic nanodomains.

## Key facts

- **NIH application ID:** 10928802
- **Project number:** 5F99NS135807-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Zoila Maribel Estrada-Tobar
- **Activity code:** F99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $42,826
- **Award type:** 5
- **Project period:** 2023-09-15 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10928802

## Citation

> US National Institutes of Health, RePORTER application 10928802, Role of PSD-95-linked PDE4A5 in Regulation of AMPA Receptors (5F99NS135807-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10928802. Licensed CC0.

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