# Regulation of Axonal Transport by Tau

> **NIH NIH R01** · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · 2022 · $392,391

## Abstract

Tau is a microtubule associated protein (MAP) primarily expressed in neurons that has
traditionally been thought to promote microtubule assembly and stability in the axon.
However, recent in vitro motility experiments have also demonstrated that Tau is a
potent inhibitor of processive kinesin movement along microtubules. These results
present an interesting paradox, namely – how can kinesin processively transport its
cargo along microtubules in the presence of Tau, which is highly expressed in neurons
and localized to the axon? The answer to this question has important implications for
axonal transport, a critical process in neurons required for the efficient delivery of
organelles, proteins, nucleic acids, and small molecules synthesized in the cell body to
their site of function in distal regions of the axon. Defects in any one of the protein
components in the axonal transport machinery, which includes microtubules, members
of the kinesin superfamily of motor proteins, a variety of adapter molecules that link
kinesin to its intracellular cargo, and MAPs such as Tau, result in serious and often lethal
neurodegenerative diseases, including Alzheimer's, Parkinson's, Huntington's, and ALS.
This proposal will elucidate the mechanistic basis for isoform specific differences in
Tau's ability to modulate the processive motility of the major molecular motors involved
in axonal transport, including kinesin-1, kinesin-2, and kinesin-3, as well as cytoplasmic
dynein. Additionally, the effects of phosphorylation of Tau at physiologically-relevant and
pathogenic sites on motor protein function and microtubule organization and architecture
will be examined in in vitro cellular and reconstituted protein experiments using state-of-
the art single molecule imaging techniques.

## Key facts

- **NIH application ID:** 10399546
- **Project number:** 5R01GM132646-04
- **Recipient organization:** UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
- **Principal Investigator:** CHRISTOPHER L. BERGER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $392,391
- **Award type:** 5
- **Project period:** 2019-07-15 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10399546

## Citation

> US National Institutes of Health, RePORTER application 10399546, Regulation of Axonal Transport by Tau (5R01GM132646-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10399546. Licensed CC0.

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