# Dystrophin domains required for microtubule lattice organization

> **NIH NIH F31** · UNIVERSITY OF MINNESOTA · 2020 · $17,561

## Abstract

PROJECT SUMMARY
Dystrophin is a large protein that functions to connect the intracellular actin cytoskeleton to the sarcolemma
and ultimately to the extracellular matrix via the dystrophin-glycoprotein complex. Striated muscle can lose
functional dystrophin protein due to an array of mutations that result in Duchenne muscular dystrophy (DMD).
As a disease with no cures, DMD is typically fatal by the third decade of life even with palliative care. One
promising treatment under development for DMD is gene therapy. However, truncated dystrophin constructs
are most typically utilized due to the large size of the dystrophin gene. The dystrophin deficient mdx mouse
exhibits a disorganized microtubule lattice that is associated with greatly reduced ability to generate force
following eccentric contraction. My preliminary data reveal that miniaturized dystrophins are not able to protect
the sub-sarcolemmal microtubule lattice against the stress imposed by eccentric contraction. The objective of
this study is therefore to mechanistically assess how dystrophin influences microtubules in vivo in both resting
and eccentrically contracted muscle. In aim 1, truncated dystrophins expressed on the mdx background will be
utilized to define which dystrophin domains regulate microtubule stability in unstressed and eccentrically
contracted muscle. Domain analysis will be paired with an iTRAQ proteomic screen to identify intermediary
proteins regulating microtubule organization. In aim 2, the physiological parameters influencing eccentric
contraction induced microtubule loss will be determined as well as the dynamics of microtubule recovery over
time.

## Key facts

- **NIH application ID:** 9950846
- **Project number:** 5F31AR073629-03
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** D'anna M Nelson
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $17,561
- **Award type:** 5
- **Project period:** 2018-06-13 → 2020-09-11

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9950846

## Citation

> US National Institutes of Health, RePORTER application 9950846, Dystrophin domains required for microtubule lattice organization (5F31AR073629-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9950846. Licensed CC0.

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