# The circadian clock protein BMAL and post-translational regulation of ENaC in the kidney

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2023 · $335,500

## Abstract

ABSTRACT
The epithelial sodium channel (ENaC) expressed in the distal tubule and collecting duct
is responsible for the final regulation of sodium reabsorption by the kidneys. The
myristoylated alanine-rich C kinase substrate (MARCKS) plays an important role as an
adaptor protein between the anionic phospholipid PIP2 and ENaC. Both ENaC and
MARCKS are positively regulated by the protease cathepsin B. First, our preliminary
data demonstrate renal ENaC activity and MARCKS protein expression are positively
regulated by the circadian protein BMAL1. Second, our preliminary data show alpha-1
antitrypsin is increased in the BMAL1 knockout mouse kidney compared to the kidney of
wild-type mice sacrificed at the same time. Third, our preliminary data show alpha-1
antitrypsin is expressed in the kidney and it strongly inhibits cathepsin B activity and
contributes to blood pressure regulation. In this project we will test our hypothesis that
the association between renal ENaC and MARCKS, and their function at the apical
plasma membrane negatively correlates with alpha-1 antitrypsin expression in a
circadian dependent manner. We will perform experiments to investigate proteolysis
and apical membrane expression of ENaC and MARCKS, ENaC activity, sodium
handling, and blood pressure using male and female BMAL1 knockout mice, alpha-1
antitrypsin knockout mice, alpha-1 antitrypsin overexpressing mice, cathepsin B
knockout mice, and wild-type control mice. The successful completion of our proposed
studies for this project will reveal new mechanisms underlying the role of BMAL1 in the
regulation of renal ENaC and MARCKS and blood pressure control. Our long term goal
is to provide a better understanding for the pathogenesis of essential hypertension that
can potentially lead to novel drug targets and therapeutics.

## Key facts

- **NIH application ID:** 10662317
- **Project number:** 5R01DK123078-04
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Abdel Ayube Alli
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $335,500
- **Award type:** 5
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10662317

## Citation

> US National Institutes of Health, RePORTER application 10662317, The circadian clock protein BMAL and post-translational regulation of ENaC in the kidney (5R01DK123078-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10662317. Licensed CC0.

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