# Mechanism of myosin motor-dependent filopodia formation

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2020 · $137,715

## Abstract

Parent Grant Abstract/Summary
 Cells migrating in tissues use filopodia to interact with and move through their 3D
environment. Filopodia are slender actin-filled projections composed of a core of cross-linked,
parallel actin bundles. They are highly dynamic, vary in length and are found in a wide variety
of cell types such as neurons that use them for gradient sensing and efficient directional
migration and cancer cells that employ them for invading into neighboring tissue.
 The mechanism of filopodia initiation is not well understood. Three conserved proteins are
required for their formation - a MyTH4-FERM myosin (MF; MyTH4 = myosin tail homology 4;
FERM = band 4.1, ezrin, radixin, moesin) and two regulators of actin polymerization, VASP and
Formin. How the action of these three proteins is coordinated to generate filopodia is unknown.
The objective of the parent project is to define the molecular mechanism of filopodia initiation
with an emphasis on the role of a MF myosin in this process. The versatile model system,
Dictyostelium will be used to define how a MF myosin and VASP work together to organize the
fast growing ends of actin filaments at the membrane to initiate construction of an actively
extending actin filament bundle. A combination of in vivo, in vitro and in silico approaches are
proposed to a) determine the functional relationship between a MF myosin, VASP and formin, b)
identify the specific properties of the myosin motor used for filopodia initiation, c) identify
proteins that interact with the MF myosin to promote cortical targeting during filopod initiation
and filopod tip formation and d) develop a stochastic computational model with predictive power
that will inform the experimental goals, the results of which will be used to refine the model.
 The knowledge generated from the parent project will reveal how cells use a myosin-based
motor to build specific actin-based structures such as filopodia. Understanding how initiation
occurs will also reveal how cells control filopodia formation to enable directed migration or
invasion of surrounding tissues.

## Key facts

- **NIH application ID:** 10135339
- **Project number:** 3R01GM122917-03S2
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** MARGARET A TITUS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $137,715
- **Award type:** 3
- **Project period:** 2017-09-15 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10135339

## Citation

> US National Institutes of Health, RePORTER application 10135339, Mechanism of myosin motor-dependent filopodia formation (3R01GM122917-03S2). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10135339. Licensed CC0.

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