# The mechanisms regulating actin dynamics and polarized membrane transport during invadopodia formation

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2020 · $87,000

## Abstract

Project Summary
Remodelling of the extracellular matrix (ECM) is a key process in cell migration during normal development as
well as during cancer metastasis. This ECM remodelling is mediated via formation of structures, known as
invadopodia and targeted secretion of enzymes, known as matrix metalloproteinases (MMPs). Invadopodia
extension and degradation of ECM is dependent on coordinated localized actin polymerization as well as
targeted secretion of MMPs at the tips of the invadopodia, which ultimately leads to cell migration. However,
little is known about the mechanisms mediating targeted MMP secretion and how MMP secretion and actin
dynamics are coordinated during cell migration. We recently identified Rab40b as a key regulator of targeted
MMP secretion and invadopodia extension in breast cancer cells. We have shown Tks5 and SGEF are Rab40b
binding proteins. Significantly, Tks5 and SGEF are both actin and in invadopodia regulating proteins.
Additonally, we also demonstrated that Cullin-5 protein also binds to Rab40b and possibly mediate
ubiquitination/degradation of invadopodia regulating proteins. Based on all these data, we propose the
following specific hypotheses: (1) Rab40b binding to SGEF coordinates actin polymerization and MMP
secretion at the invadopodia during cell migration through the ECM; (2) Cullin-5 binding to Rab40b regulates
invadopodia formation and function during cell migration. The goal of this project is to directly test these
hypotheses. First, we will define the roles of Rab40b and SGEF complex in regulating actin dynamics during
invadopodia formation and cell migration in vitro. Second, we will elucidate the role of Cullin-5 binding to
Rab40b in terminating invadopodia formation and cell migration. Third, we will test Rab40b role in regulating
actin dynamics and cell migration in vivo. To that end, we will use neural crest cell migration during zebrafish
development as experimental model that will allow us to analyse cell migration and ECM remodelling in live
cells during embryogenesis. In summary, completion of this study will define new machinery governing and
coordinating polarized membrane transport, cytoskeleton dynamics and ECM remodelling during cell migration
in development and carcinogenesis.

## Key facts

- **NIH application ID:** 10130137
- **Project number:** 3R01GM122768-03S1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Rytis Prekeris
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $87,000
- **Award type:** 3
- **Project period:** 2018-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10130137

## Citation

> US National Institutes of Health, RePORTER application 10130137, The mechanisms regulating actin dynamics and polarized membrane transport during invadopodia formation (3R01GM122768-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10130137. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*