# Functional Substructure of Flagellar Dynein

> **NIH NIH R01** · EMORY UNIVERSITY · 2020 · $377,812

## Abstract

Project Summary/Abstract
The overall goal of our work is to understand the assembly and regulation of motile cilia. Cilia play vital motile
and signaling roles in virtually every differentiated cell. As a consequence, failure in conserved assembly
mechanisms, including the transport machine IFT (intraflagellar transport) and assembly of dynein motors,
results in a wide range of human diseases including primary cilia dyskinesia (PCD) and consequences for
development and adult organ function. Although we have a good understanding of ciliary structure and dynein
motor organization, we are only beginning to understand how the dynein motor complexes are transported and
assembled. Gaps in knowledge include steps and factors required for cytoplasmic “preassembly” of axonemal
dyneins, transport into the ciliary compartment, loading of complexes on IFT and regulation of transport,
regulation of cargo-IFT unloading and targeting and docking of complexes on outer doublet microtubules in a
96nm repeat organization. The current focus of our work is on assembly of the ciliary axonemal inner dynein
arm called I1 dynein, also known as dynein f, as an ideal model for axonemal dynein transport and assembly in
the axoneme. I1 dynein is a large, conserved, two-headed inner dynein arm that is required for normal ciliary
movement and regulation of axonemal bending. I1 dynein is a “slow”, possibly non-canonical, axonemal
dynein thought to resist microtubule sliding driven by other “fast“ axonemal dyneins. As such, I1 dynein, plays
a critical role in control of axonemal bending and waveform. We have also determined that I1 dynein is
preassembled in the cytoplasm, transported by IFT and targeted to a unique position repeating every 96 nm
along each of the doublet microtubule, and assembles independent of the assembly of the other dyneins. Here
we will address the transport of I1 dynein, as a cargo for IFT, and test the hypothesis that the Chlamydomonas
IDA3 gene, which encodes a coiled-coil protein, Ida3, is specifically required for IFT transport of I1 dynein (Aim
1). We also test the hypothesis that the intermediate chain IC140 interacts with a docking protein or proteins
for localization of I1 on the doublet microtubule (Aim 2). From this new work, we will learn how dyneins, as
cargoes, are transported to and within cilia, and address the principle that each axonemal complex (e.g.
dyneins, radial spokes, N-DRC) require specialized adaptors or regulators for directed transport. In addition,
we will, for the first time, learn how an axonemal inner dynein arm is localized in the 96 nm repeat.

## Key facts

- **NIH application ID:** 9830646
- **Project number:** 5R01GM051173-35
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** WINFIELD S SALE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $377,812
- **Award type:** 5
- **Project period:** 1985-07-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9830646

## Citation

> US National Institutes of Health, RePORTER application 9830646, Functional Substructure of Flagellar Dynein (5R01GM051173-35). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9830646. Licensed CC0.

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