# Mechanisms of the unusual cytokinesis in trypanosomes

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2021 · $446,186

## Abstract

Cytokinesis in Trypanosoma brucei, a parasitic protozoan and the causative agent of human sleeping
sickness, is initiated from the anterior tip of the new flagellum attachment zone (FAZ) filament. The cytokinesis
cleavage furrow ingresses uni-directionally along the longitudinal axis from the anterior towards the posterior
end of the cell, without the involvement of an actomyosin contractile ring, which appeared after T. brucei
diverged from the last eukaryotic common ancestor. Cytokinesis in T. brucei is known to be totally different
from that in its human host, and therefore is a promising drug target. It is believed that the cytokinesis
regulatory pathway in T. brucei is different from most eukaryotes and that the cleavage furrow in T. brucei
involves novel components. However, little is known about the cytokinesis regulatory pathway and the
cleavage furrow components in T. brucei, thus significantly hindering our understanding of the mechanisms of
cytokinesis in this dreadful human pathogen. The current proposal is built upon the recently discovered cytokinesis signaling cascade, and aims to address the following questions. (1). What are the cytokinesis signaling pathways in different life cycle forms of T. brucei? We hypothesize that multiple regulators, including evolutionarily conserved protein kinases and kinetoplstid-specific regulators, cooperate at the anterior tip of the new FAZ filament to regulate cytokinesis initiation and at the cleavage furrow to promote cleavage furrow ingression. Our focus is on the mechanistic
roles of two novel proteins, named CIF3 and CIF4, in cytokinesis and how they cooperate with the known
cytokinesis regulators to fulfil their biological function in both the insect and bloodstream forms. (2). What are
the physiological roles of protein phosphorylation and dephosphorylation in cytokinesis? The involvement of
two protein kinases, TbPLK and TbAUK1, in cytokinesis suggests an extensive phosphorylation of cytokinesis
regulators by the two kinases. Importantly, we identified a kinetoplastid-specific protein phosphatase, named
KPP1 (Kinetoplstid-specific Protein Phosphatase 1), that appears to antagonize TbPLK. We propose to
investigate the physiological roles of CIF1 and CIF2 phosphorylation by TbPLK and TbAUK1 and the
contribution of KPP1 to cytokinesis. (3). What drives cleavage furrow ingression and what are the components
of the cleavage furrow? We identified a novel protein that contains a kinesin motor domain and two
tropomyosin domains and localizes to the cleavage furrow during cytokinesis. We thus hypothesize that T.
brucei employs a novel tropomyosin-based contractile machinery for furrow ingression and a plus end-directed
kinesin motor to drive the uni-directional furrow ingression from the anterior cell end (minus end of the
microtubules) toward the posterior cell end (plus ends of the microtubules).  The long-term goal of my laboratory is to delineate the regulatory pathway that controls cytokines...

## Key facts

- **NIH application ID:** 10179302
- **Project number:** 5R01AI101437-09
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Ziyin Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $446,186
- **Award type:** 5
- **Project period:** 2013-06-06 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10179302

## Citation

> US National Institutes of Health, RePORTER application 10179302, Mechanisms of the unusual cytokinesis in trypanosomes (5R01AI101437-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10179302. Licensed CC0.

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