# Regulation of cytokinesis by cell polarity signaling

> **NIH NIH R01** · DARTMOUTH COLLEGE · 2021 · $328,000

## Abstract

Cell polarity orients cytoskeletal filaments toward spatial landmarks, directing local cell growth.
Protein kinases play key roles in cell polarity by translating spatial signals into regulation of
cytoskeletal proteins including actin and myosin. At cell division, the actomyosin machinery
dramatically reorganizes into a cytokinetic ring that constricts to separate the dividing cells. We
hypothesize that cell polarity kinases act directly on the contractile actomyosin ring (CAR) to
promote its assembly, organization, and function in cytokinesis. In this model, cell polarity
signaling proteins regulate the CAR in cytokinesis analogous to their roles on other actomyosin
structures in polarized growth. We study cell polarity and cytokinesis using the fission yeast S.
pombe as a model system because it offers a well-defined parts list and a host of experimental
advantages. Our preliminary data show that three conserved cell polarity protein kinases—Pak1,
Kin1, and Pom1—directly phosphorylate CAR proteins and regulate specific steps in CAR
assembly and constriction during cell division. In addition, regulators of the phosphatase PP2A
are required to keep the CAR anchored in the correct place during cytokinesis. We propose to
understand the molecular mechanisms by which these conserved protein kinases and
phosphatases act on the CAR to promote cell division. The specific aims of this grant are to: (1)
determine how Pak1 regulates the cytoskeleton during cell division, (2) test the hypothesis that
Pom1, Kin1, and Pak1 represent sequential regulatory inputs for cytokinesis proteins, and (3)
investigate how regulation of PP2A phosphatase positions the CAR. Successful completion of
these goals will define a signaling system that prevents defects in cell division, and will identify
previously unknown connections between two fundamental cellular processes: cell polarity and
cytokinesis.

## Key facts

- **NIH application ID:** 10223377
- **Project number:** 5R01GM133856-03
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** James B Moseley
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $328,000
- **Award type:** 5
- **Project period:** 2019-09-15 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10223377

## Citation

> US National Institutes of Health, RePORTER application 10223377, Regulation of cytokinesis by cell polarity signaling (5R01GM133856-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10223377. Licensed CC0.

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