# Regulation of TRPM7 Channels

> **NIH NIH R01** · RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL · 2020 · $11,615

## Abstract

PROJECT SUMMARY
Excessive TRPM7 channel activity is linked to neuronal cell death, cancer cell metastasis, and as our
preliminary data will demonstrate, the development of cardiac fibrosis in a hypertensive hypertrophy/heart
failure mouse model. Collectively, these findings underscore a critical role for TRPM7 in the pathology of a
multitude of diseases, making channel an attractive target for therapeutic intervention. However, the specific
mechanisms controlling TRPM7 activity in vivo remain unknown. We have made the critical discovery that
TRPM7 binds to CNNM proteins (CNNM1-4), which our preliminary data indicate function as regulatory
subunits of the channel. We further show that PTP4A phosphatases activate TRPM7 in a CNNM-dependent
manner. TRPM7 is the first identified ion channel to possess a kinase domain, the function of which is poorly
understood. We recently reported the discovery that auto-phosphorylation of the channel plays a decisive role
in controlling the stability of TRPM7 protein expression and the channel's localization in cells. We hypothesize
that PTP4A phosphatases, CNNMs, and channel phosphorylation operate in concert to regulate TRPM7. In the
multi-PI proposal, we propose three specific aims to elucidate the molecular mechanisms controlling the
TRPM7 channel with the long-term goal of understanding how the channel becomes upregulated during
cardiac fibrosis. In specific aim 1, we will employ electrophysiology, imaging, and biochemical approaches to
elucidate the regulation of TRPM7 by CNNMs and PTP4As. In specific aim 2, we will apply analytical mass
spectrometry, biochemical, and imaging approaches to understand how phosphorylation of the channel
regulates TRPM7 protein expression and its cellular localization. In specific aim 3, we will investigate the
specific mechanism(s) controlling pathological stimulation of the channel during cardiac fibrosis. There is an
urgent need for new treatments for stroke, cancer, and heart disease, which kill or severely disable millions of
individuals each year. Results from our investigation will have a significant impact by uncovering the
mechanisms controlling the channel, which may lead to novel clinical approaches for blocking TRPM7's
pathological actions in these devastating diseases.

## Key facts

- **NIH application ID:** 9974402
- **Project number:** 3R01HL147350-01S1
- **Recipient organization:** RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL
- **Principal Investigator:** LOREN W RUNNELS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $11,615
- **Award type:** 3
- **Project period:** 2019-04-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9974402

## Citation

> US National Institutes of Health, RePORTER application 9974402, Regulation of TRPM7 Channels (3R01HL147350-01S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9974402. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*