# Identifying the Mechanism for Outer Arm Dynein Coordination in Ciliary Motion

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA BERKELEY · 2020 · $64,926

## Abstract

Project Summary
 Motile cilia are hair-like protrusions from the cell surface that beat in a sinusoidal waveform to produce
movement. This movement is responsible for the flow of mucus through the respiratory tract, organ left-right
asymmetry, and sperm motility. Each cilium is composed of nine rigid tubular structures called microtubule (MT)
doublets arranged in a circle around a single central pair of MTs. Microtubule motors called outer arm dyneins
(OADs) slide the MT doublets relative to one another while connectors between doublets convert the sliding into
bending. The wave motion is generated as OADs on opposite sides of the cilia alternate activity down the length
of the cilium. Previous studies have shown that coordination persists in the absence of external cues. Models
propose that OAD coordination can be achieved by responding to changes in MT curvature and interdoublet
spacing during beating. Alternatively, MT sliding can regulate motor activity by generating self-organized
oscillations. However, the mechanism of OAD motility and force generation remains poorly understood in
comparison to the cytoplasmic isoform of dynein. Therefore, it remains unclear which model(s) apply to ciliary
bending
 The recent development of the recombinant expression of Tetrahymena OAD allows us to study its
mechanics for the first time. Thus far, many of the model predictions have been tested by using cytoplasmic
dynein which is structurally distinct from OAD. In contrast to cytoplasmic dynein, a homodimer, OAD forms a
heterotrimer of (α, β, and γ) heavy chains and is not processive at physiological ATP. To understand the
mechanism of dynein self-regulation in cilia, I will characterize the motility and force generation characteristics
of single OAD motors, and test how MT curvature and sliding impact OAD activity in vitro.
 The goal of this study is to directly test the specific biophysical predictions made by the models through
three core aims: First, we will test the molecular properties of OADs, such as coordination of motor stepping
along MTs and force-induced MT attachment/detachment of dynein from the MT. Second, we will construct in
vitro assays that mimic the geometries of dynein/MT interactions in a beating cilium. Third, we will use solved
structures for axonemal dynein and cytoplasmic dynein to make directed mutations to identify the structural
components of OAD that gives rise to its nonprocessive motility, curvature sensing, and oscillatory behavior.
 This work will establish an experimental and theoretical framework for the study of the molecular
mechanism of OAD and enable us to determine the minimum requirements for self-coordinated oscillation of
motile cilia.

## Key facts

- **NIH application ID:** 9992287
- **Project number:** 1F32GM136180-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Ruensern Tan
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $64,926
- **Award type:** 1
- **Project period:** 2020-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9992287

## Citation

> US National Institutes of Health, RePORTER application 9992287, Identifying the Mechanism for Outer Arm Dynein Coordination in Ciliary Motion (1F32GM136180-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9992287. Licensed CC0.

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