# Mechanistic Analysis of Cytokinesis in Eukaryotes

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2021 · $447,819

## Abstract

Project Summary/Abstract:
Cytokinesis is essential for development and survival of all organisms. Defects in cytokinesis cause
aneuploidy and genomic instability, thereby contributing to serious diseases such as cancer, neuronal
disorders, and anemia. Thus, mechanistic study of cytokinesis is important not only for understanding the
basic principles of a fundamental process but also for designing new strategies to treat human diseases.
Cytokinesis in animal and fungal cells requires spatiotemporally coordinated functions of a contractile
actomyosin ring (AMR), targeted vesicle fusion, and localized extracellular matrix (ECM) remodeling. It is
much more complex than previously appreciated. In this application, we will address three major
unanswered questions regarding this fundamental process using both budding yeast and mammalian cell
models, with the goal of dissecting deep mechanisms in yeast and exploring evolutionary conservation in
mammalian cells. In Aim 1, we will determine the architecture of the AMR. Specifically, we will examine how
myosin-II and its associated proteins such as actin and IQGAP are organized in the contractile ring from cells
synchronized at cytokinesis using platinum-replica electron microscopy (PREM) coupled with immuno-gold
labeling as well as super-resolution stochastic optical reconstruction microscopy (STORM). In Aim 2, we will
test our hypothesis that myosin filament assembly is regulated by heavy chain phosphorylation as well as by
trans-acting factors such as IQGAP using biochemical, genetic, quantitative live imaging, and other cutting-
edge imaging methods as described above. In Aim 3, we will determine how the AMR guides exocytosis
and ECM remodeling at the division site. Specifically, we will test our hypothesis that the tail of the yeast
myosin-II positions and unloads vesicles from the transport machinery at the division site by interacting with
the vesicle-associated guanine-nucleotide-exchange factor (GEF), Sec2, for the Rab GTPase Sec4. Then,
the myosin-associated protein complex (Inn1, Hof1, and Cyk3) promotes vesicle fusion via the C2 domain of
Inn1, and activates the cargo enzyme Chs2, a member of the glycosyltransferase family 2, for ECM
remodeling (i.e. septum formation in yeast) via the transglutaminase-like domain of Cyk3.
The discovery (Aim 1) and hypothesis-driven (Aims 2 and 3) research is expected to generate novel
concepts and mechanisms of cytokinesis that are beyond specific model organisms.

## Key facts

- **NIH application ID:** 10224222
- **Project number:** 5R01GM115420-07
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Erfei Bi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $447,819
- **Award type:** 5
- **Project period:** 2015-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10224222

## Citation

> US National Institutes of Health, RePORTER application 10224222, Mechanistic Analysis of Cytokinesis in Eukaryotes (5R01GM115420-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10224222. Licensed CC0.

---

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