# Renal implications of AQP3 lysine acetylation

> **NIH NIH R03** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $111,375

## Abstract

SUMMARY
Fluid-electrolyte disorders are prevalent in our society, and even mild disorders are associated
with poor outcomes. A key component of body fluid regulation is largely through control of water
reabsorption by the renal collecting duct (CD) via the actions of vasopressin. The aquaporins
(AQPs) are a large family of water channels expressed throughout the body. In the CD, there is
apical expression of AQP2 and basolateral expression of AQP3 and AQP4 that regulate
transcellular water reabsorption. AQP2 and AQP3 are vasopressin-sensitive, and genetic deletion
of either of these water channels results in severe polyuria and a urinary concentrating defect.
Compared to AQP2, we know little about the regulation of AQP3 function. We recently determined
that AQP3 can be post-translationally lysine (K) acetylated at K282. Acetylated AQP3 (acAQP3)
is expressed in the basolateral membrane of the CD and is increased with water deprivation in
both male and female mice. Moreover, acAQP3 expression increases in the inner medullary
collecting duct with dehydration. Our central hypothesis is that lysine acetylated AQP3 is critical
for maintaining fluid balance during water deprivation. Our preliminary data suggest that the
acetyltransferases CBP (CREB Binding Protein) and EP300 interact and lysine acetylate AQP3.
The focus of our “intracellular signaling aim” is to test the hypothesis that vasopressin activates
CBP and EP300 resulting in lysine acetylation of AQP3. We will also determine the functional
significance of this novel post-translational modification. The goal of the “physiology aim” is to
test the hypothesis that acetylation of AQP3 results in anti-diuresis. Identification of acetylation of
AQP3 K282 provides a new target for therapeutic interventions to treat water balance disorders.
The data, reagents, tools, and mice generated from this application are key for the successful
submission and subsequent funding of my R01 within the next two years.

## Key facts

- **NIH application ID:** 9878848
- **Project number:** 5R03DK120503-02
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Kelly Hyndman
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $111,375
- **Award type:** 5
- **Project period:** 2019-04-01 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9878848

## Citation

> US National Institutes of Health, RePORTER application 9878848, Renal implications of AQP3 lysine acetylation (5R03DK120503-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9878848. Licensed CC0.

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