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

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2022 · $428,731

## 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. 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 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 by the concerted action of
simultaneously bound, opposite polarity motors, in a process called bidirectional transport. How
individual motors are recruited to cargo, activated, and integrated with other classes of motors
presents a large open challenge to the field. Importantly, defects in this process lead to a wide variety
of human diseases and these questions are thus directly related to human health.
 Microtubule network organization, dynamics, and motor activity along microtubules are all
impinged upon by non-enzymatic microtubule-associated proteins (MAPs) that dynamically bind to
microtubules. The specific functions, molecular properties, and dynamics of MAPs remains
underexplored. The tau family of MAPs are critically important for human health, as tau is well-
characterized to form insoluble inclusions/aggregates in a host of human neurodegenerative diseases
such as Alzheimer’s disease and Pick’s disease. Despite their identification over four decades ago,
the specific molecular functions and molecular properties of tau family MAPs remains unclear. This
application seeks to develop novel assays and tools to study the complexity of microtubule motor
regulation, bidirectional transport of cargos, and cytoskeletal functions driven by motors and MAPs.
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 native cellular cargo scaffolding molecules, and 2) Reconstitute and study
evolutionary functions, dynamics, and pathological behaviors of tau family MAPs. These broad goals
build and expand upon our expertise and previous work in dissecting the regulatory mechanisms of
the cytoplasmic dynein motor, and aim to provide powerful new tools useful towards dissectin...

## Key facts

- **NIH application ID:** 10406085
- **Project number:** 2R35GM124889-06
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Richard James McKenney
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $428,731
- **Award type:** 2
- **Project period:** 2017-09-30 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10406085

## Citation

> US National Institutes of Health, RePORTER application 10406085, Coordination of molecular motor activity in intracellular transport and assembly of cytoskeletal archit (2R35GM124889-06). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10406085. Licensed CC0.

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