# Function of Ruvbl1-Ruvbl2 in dynein arm assembly in motile ciliated epithelial cells

> **NIH NIH R01** · YALE UNIVERSITY · 2024 · $701,440

## Abstract

Motile cilia beat rhythmically to propel cell movement or drive extracellular fluid flow. The functional importance
of cilia motility in human health is highlighted by primary ciliary dyskinesia (PCD), a genetic disease caused by
cilia motility defects. Patients with PCD display left-right asymmetry defect, reduced fertility and progressive lung
disease. Currently there is no specific therapy for PCD and management of symptoms has been the main
approach. The dynein arms that power cilia motility comprise multiple components that are pre-assembled in the
cytosol and many genes associated with PCD encode components of dynein arms. A separate group encode
dynein arm assembly factors (DNAAFs), proteins that reside in the cytosol and facilitate the assembly of dynein
arm subunits. Interestingly, multiple DNAAFs are localized in droplet shaped cytosolic foci. However, the precise
function of these foci and the precise molecular function of most DNAAFs remain poorly understood. Based on
extensive preliminary and published data, our central hypothesis is that the co-chaperone proteins Ruvbl1 and
Ruvbl2 are core components of a novel membrane-less cytosolic assemblage that functions to coordinate the
translation, folding and assembly of axonemal dynein arm components. In this project, we will combine zebrafish
genetics, mouse genetics and cultured tracheal cells to test our central hypothesis. We propose two specific
aims to achieve this goal. In the first aim, we will dissect the mechanism of Ruvbl1-Ruvbl2 foci formation. In the
second aim, we will systematically define R2HAD components and dissect their biochemical and functional
relationships with DNAAFs associated with PCD. Successful completion of this project will not only provide a
molecular framework for dynein arm assembly and the etiology of PCD, but also lay the foundation for future
investigation into the regulation, and possible intervention, of dynein arm assembly and cilia motility under
diverse physiological and disease conditions.

## Key facts

- **NIH application ID:** 10945178
- **Project number:** 1R01HL175156-01
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** ZHAOXIA SUN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $701,440
- **Award type:** 1
- **Project period:** 2024-09-01 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10945178

## Citation

> US National Institutes of Health, RePORTER application 10945178, Function of Ruvbl1-Ruvbl2 in dynein arm assembly in motile ciliated epithelial cells (1R01HL175156-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10945178. Licensed CC0.

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