# Mechanism of Microtubule Dynamics Regulation by Kinesins

> **NIH NIH R01** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2021 · $442,550

## Abstract

Kinesins are eukaryotic cytoskeletal proteins best known for their motile activity, but they are
also important regulators of microtubule dynamics, the ability of the microtubule polymer to grow
or shrink. This project seeks to establish the molecular mechanism of microtubule dynamics
regulation by members of the kinesin superfamily. Regulation of microtubule dynamics by these
kinesins play important roles in a variety of cell processes such as mitosis, cytokinesis, neural
development and control of cilia and centriole length, but the mechanisms by which these
kinesins stabilize or destabilize microtubules is still not clear. It is not known how different
kinesin may be adapted for seemingly different functionalities or whether they share common
mechanisms. To address this issue we propose to conduct comparative structural and
functional analysis of several kinesins with distinct functionalities: the microtubule depolymerase
KLP10A (kinesin-13), the motile and microtubule stabilizers KIF14 (kinesin-3) and EG5 (kinesin-
5) and the archetypical motile kinesin KIF5B (kinesin-1). The proposal is divided in four aims.
The first two aims test the hypothesis based on our recent work that the same ATPase related
confomational changes occurring in the motor domain of kinesin-1s are adapted in kinesin-13s
to depolymerize microtubules. The second aim investigates the mechanism by which EG5
promotes microtubule polymerization and inhibits depolymerization. The fourth aim uses cryo-
em structural analysis to guide the development and optimization of KIF14 specific drugs for
research and potentially clinical use.

## Key facts

- **NIH application ID:** 10092172
- **Project number:** 5R01GM113164-09
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** HERNANDO Jose SOSA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $442,550
- **Award type:** 5
- **Project period:** 2015-03-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10092172

## Citation

> US National Institutes of Health, RePORTER application 10092172, Mechanism of Microtubule Dynamics Regulation by Kinesins (5R01GM113164-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10092172. Licensed CC0.

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