# Investigating mechanisms of neuronal nuclear mechanotransduction in physiological conditions and tauopathy

> **NIH NIH F31** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2024 · $38,674

## Abstract

PROJECT SUMMARY
Mechanotransduction is the ability of a cell to detect and respond to mechanical stimuli. This tightly regulated
process allows cells to adapt to environmental and structural changes. The nucleus is a central regulator of
mechanotransduction. As the nucleus detects a change of force, it responds by altering cell behavior and
function. While extensive research in non-neuronal cell types has investigated mechanotransduction in the
context of cell proliferation, metastasis, and differentiation within physiological and pathological conditions, few
studies have investigated the role of mechanotransduction in neurons. The brain is exposed to changes in
mechanical force from the vasculature, direct force impacts with the skull, and neurodegeneration. Tauopathies,
including Alzheimer’s disease, are neurodegenerative disorders that involve the progressive deposition of tau
protein in the brain. Mechanistically, pathogenic forms of tau have been found to drive neurodegeneration by
inducing over-stabilization of the actin cytoskeleton, which causes destabilization of the lamin nucleoskeleton.
Nucleoskeletal destabilization drives heterochromatin decondensation, aberrant gene expression, and ultimately
neuronal death. I recently reported that neurons harboring pathological tau have a decrease in nuclear tension
and a disruption in the Linker of Nucleoskeleton to Cytoskeleton (LINC) complex, an established nuclear
mechanosensor. My preliminary studies indicate that neurons harboring pathological tau have a significant
increase of emerin, a mechanosensitive protein that resides on the inner nuclear membrane and binds to A-type
lamins. Studies in non-neuronal cells suggest that mechanical stimulation causes emerin to become
phosphorylated and translocate to the cytoplasm, where it regulates actin dynamics. As neurons predominantly
express B-type lamins, it is currently unknown if and how emerin regulates nuclear mechanotransduction in
neurons. The overall goal of this proposal is to better understand mechanisms underlying nuclear
mechanotransduction in neurons in physiological and pathological conditions. I will test the hypotheses that
emerin is mechanosensitive in neurons and interacts directly with B-type lamins, and that pathogenic forms of
tau disrupt nuclear mechanotransduction. Understanding how neurons detect and respond to mechanical forces
will be instrumental to our understanding of basic neurobiology and disease.

## Key facts

- **NIH application ID:** 10901610
- **Project number:** 1F31NS137774-01
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** Claira Rose Sohn
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $38,674
- **Award type:** 1
- **Project period:** 2024-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10901610

## Citation

> US National Institutes of Health, RePORTER application 10901610, Investigating mechanisms of neuronal nuclear mechanotransduction in physiological conditions and tauopathy (1F31NS137774-01). Retrieved via AI Analytics 2026-06-02 from https://api.ai-analytics.org/grant/nih/10901610. Licensed CC0.

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