# Regulation of cytoplasmic dynein in vivo

> **NIH NIH R01** · HENRY M. JACKSON FDN FOR THE ADV MIL/MED · 2020 · $295,139

## Abstract

Abstract
Microtubule-based intracellular transport is critical for the function of all eukaryotic cells. Cytoplasmic
dynein is a minus-end-directed microtubule motor that transports a variety of cargoes, and dynein-cargo
interactions require the dynactin complex and specific cargo adapters. How dynein-cargo interactions are
regulated in vivo and how dynein activity is coordinated with cargo binding are major open questions in
the field. Recently, structural studies and in vitro motility assays led to the hypothesis that the binding of
cargo to the pointed end of dynactin's Arp1 filament may unlock dynactin's p150 subunit via a change in
its conformation, leading to dynein activation. However, in vivo evidence supporting this hypothesis is
missing and the identity of proteins involved in p150's conformational change remain to be defined. We
previously found that dynactin's pointed-end protein p25 in Aspergillus nidulans is important for dynein-
early endosome interaction. Recently, we discovered that p25 is required for the interaction between
dynein-dynactin and HookA, the early endosome dynein adapter. Based on our recent data, we
hypothesize that p25 is a key protein regulating dynactin conformation. Specific Aim 1 is to reveal the
roles of dynactin p25 and the cargo adapter HookA in regulating dynactin. Sensitized emission-based
FRET imaging, microtubule pelleting and in vitro motility assays will be used to achieve this aim. In
addition, our recent genetic work has uncovered a vezatin-like protein, VezA, as a novel regulator for
dynein-cargo interaction. VezA is not a cargo adapter like HookA but affects the accumulation of dynein
at the cargo-loading site, the microtubule plus end. How VezA regulates dynein remains a mystery.
Specific Aim 2 is to determine the mechanism of VezA action in dynein-mediated vesicle transport. We
will use proteomic and genetic approaches to identify new players in the VezA-dynein pathway.

## Key facts

- **NIH application ID:** 9917794
- **Project number:** 5R01GM121850-04
- **Recipient organization:** HENRY M. JACKSON FDN FOR THE ADV MIL/MED
- **Principal Investigator:** XIN XIANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $295,139
- **Award type:** 5
- **Project period:** 2017-05-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9917794

## Citation

> US National Institutes of Health, RePORTER application 9917794, Regulation of cytoplasmic dynein in vivo (5R01GM121850-04). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9917794. Licensed CC0.

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