# Coordination of molecular motor activity in intracellular transport and assembly of cytoskeletal architecture.

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2021 · $368,291

## Abstract

Title: Coordination of molecular motor activity in intracellular transport and assembly of cytoskeletal
architecture.
P.I. – Richard J. McKenney
Research Summary
Intracellular transport is essential for cellular homeostasis in eukaryotes. Much of this process is
carried out by molecular motors that convert the chemical energy from ATP hydrolysis into motion
along the actin and microtubule cytoskeletal networks. Decades of research has uncovered structural
and molecular details that explain how many of these motors move along their filament tracks in
isolation. In the cellular milieu, most of these motors act in concert with complex regulatory machinery
that links them to their respective cargos, modulates their motile properties, and dictates
spatiotemporal activity. How individual motor output is controlled by this machinery is currently not
clear and difficult to dissect in the complex environment of the cell. In addition, many cargos are
moved simultaneously by motors of opposite polarity, in a process called bidirectional transport. How
individual motors are recruited to cargo, activated, and integrated with other classes of motors
presents a large challenge to the field. Further, the activities of disparate motors are harnessed to
build and maintain critical cytoskeletal structures such as the mitotic spindle, cilium, and cleavage
furrow. How motor and regulatory activities are coordinated to drive the self-assembly of such
structures is currently a significant barrier to understanding normal and diseased cellular physiology.
This application seeks to develop novel assays and tools to study the complexity of motor recruitment
and regulation, bidirectional transport of cargos, and the self-assembly of cytoskeletal structures
driven by motors and associated molecules. Our approach to combine biochemistry and single-
molecule analysis towards in vitro reconstitutions that test molecular function, and translate our
findings into in vivo systems that test hypotheses generated by these reconstitutions, will open up
fruitful long-term avenues of research. We propose to: 1) Reconstitute and study the recruitment,
regulation, and motility of cytoplasmic dynein and kinesin motors bound to membranous cargo
through the endogenous Rab GTPase machinery that is known to link these motors to endocytic
vesicles and mitochondria in cells, and 2) Reconstitute and study functions of dynein and kinesin
motors that drive the self-assembly of the mitotic spindle. These broad goals build and expand on our
expertise and previous work in dissecting the regulatory mechanisms of the cytoplasmic dynein motor,
and aim to provide powerful new tools useful towards dissecting complex motor function. Our work
will illuminate basic molecular and cell biological principles that drive cellular homeostasis and
provide insight into the pathological mechanisms that arise from molecular motor malfunction.

## Key facts

- **NIH application ID:** 10201652
- **Project number:** 5R35GM124889-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Richard James McKenney
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $368,291
- **Award type:** 5
- **Project period:** 2017-09-30 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10201652

## Citation

> US National Institutes of Health, RePORTER application 10201652, Coordination of molecular motor activity in intracellular transport and assembly of cytoskeletal architecture. (5R35GM124889-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10201652. Licensed CC0.

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